In vitro antiamnesic activity was evaluated against HK-9 strain of Entamoeba histolytica
|
Entamoeba histolytica
|
0.22
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, characterisation and antiamoebic activity of new thiophene-2-carboxaldehyde thiosemicarbazone derivatives and their cyclooctadiene Ru(II) complexes.
Year : 2001
Volume : 11
Issue : 20
First Page : 2675
Last Page : 2678
Authors : Shailendra NS, Bharti N, Gonzalez Garza MT, Cruz-Vega DE, Castro Garza J, Saleem K, Naqvi F, Azam A.
Abstract : Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where TSC=thiosemicarbazone). All the compounds have been characterised by elemental analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is concluded that the thionic sulphur and the azomethine nitrogen atom of the ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK-9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the thiosemicarbazones.
In vitro antiprotozoal activity against Entamoeba histolytica
|
Entamoeba histolytica
|
350.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives.
Year : 2001
Volume : 11
Issue : 2
First Page : 187
Last Page : 190
Authors : Navarrete-Vázquez G, Cedillo R, Hernández-Campos A, Yépez L, Hernädez-Luis F, Valdez J, Morales R, Cortés R, Hernández M, Castillo R.
Abstract : 2-(Trifluoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6-positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamnoeha histolytica. and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their effect on tubulin polymerization and none inhibited tubulin polymerization.
Tested for antiamnesic activity against HK-9 strain of Entamoeba histolytica
|
Entamoeba histolytica
|
0.33
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives.
Year : 2000
Volume : 10
Issue : 20
First Page : 2243
Last Page : 2245
Authors : Bharti N, Maurya MR, Naqvi F, Azam A.
Abstract : Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.
The compound was tested in vitro against the protozoa Entamoeba histolytica, for the inhibition of tubulin polymerization in rat brain
|
Entamoeba histolytica
|
350.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiparasitic activity of 1H-benzimidazole derivatives.
Year : 2002
Volume : 12
Issue : 16
First Page : 2221
Last Page : 2224
Authors : Valdez J, Cedillo R, Hernández-Campos A, Yépez L, Hernández-Luis F, Navarrete-Vázquez G, Tapia A, Cortés R, Hernández M, Castillo R.
Abstract : Compounds 1-18 have been synthesized and tested in vitro against the protozoa Giardia lamblia, Entamoeba histolytica and the helminth Trichinella spiralis. Inhibition of rat brain tubulin polymerization was also measured and compared for each compound. Results indicate that most of the compounds tested were more active as antiprotozoal agents than Metronidazole and Albendazole. None of the compounds was as active as Albendazole against T. spiralis. Although only compounds 3, 9 and 15 (2-methoxycarbonylamino derivatives) inhibited tubulin polymerization, these were not the most potent antiparasitic compounds.
Antiprotozoal activity against Trichomonas vaginalis
|
Trichomonas vaginalis
|
286.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids.
Year : 2008
Volume : 18
Issue : 11
First Page : 3147
Last Page : 3151
Authors : Torres-Gómez H, Hernández-Núñez E, León-Rivera I, Guerrero-Alvarez J, Cedillo-Rivera R, Moo-Puc R, Argotte-Ramos R, Rodríguez-Gutiérrez Mdel C, Chan-Bacab MJ, Navarrete-Vázquez G.
Abstract : A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)<1 microM) against the first four protozoa, which make them significantly more potent than either standard. 1,5-bis[4-(5-methoxy-1H-benzimidazole-2-yl)phenoxy]pentane (2) was 3- and 9-fold more potent againstG. lamblia than metronidazole and pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.
Antiprotozoal activity against Entamoeba histolytica
|
Entamoeba histolytica
|
771.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids.
Year : 2008
Volume : 18
Issue : 11
First Page : 3147
Last Page : 3151
Authors : Torres-Gómez H, Hernández-Núñez E, León-Rivera I, Guerrero-Alvarez J, Cedillo-Rivera R, Moo-Puc R, Argotte-Ramos R, Rodríguez-Gutiérrez Mdel C, Chan-Bacab MJ, Navarrete-Vázquez G.
Abstract : A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)<1 microM) against the first four protozoa, which make them significantly more potent than either standard. 1,5-bis[4-(5-methoxy-1H-benzimidazole-2-yl)phenoxy]pentane (2) was 3- and 9-fold more potent againstG. lamblia than metronidazole and pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS trophozoites after 48 hrs by MTT/PMS assay
|
Entamoeba histolytica HM-1:IMSS
|
0.04
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiprotozoal activity of the constituents of Conyza filaginoides.
Year : 2001
Volume : 64
Issue : 5
First Page : 671
Last Page : 673
Authors : Calzada F, Cedillo-Rivera R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Conyza filaginoides led to the isolation of three new flavonol caffeoyl glycosides, namely, kaempferol 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (1), isorhamnetin 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (2), and quercetin 3-O-(6' '-O-E-caffeoyl)-beta-D-glucopyranoside (3). In addition, seven known compounds, erythrodiol (4), beta-caryophyllene-4,5-alpha-oxide (5), astragalin (6), isoquercitrin (7), nicotiflorin (8), narcissin (9), and rutin (10), were obtained. The structures of the new isolates were elucidated by spectroscopic and chemical methods. Compounds were also assessed for antiamoebic and antigiardial activities, but none was significantly active compared to the standard drugs evaluated.
Antiprotozoal activity against Giardia lamblia IMSS:0989:1 after 48 hrs by MTT/PMS assay
|
Giardia intestinalis
|
0.21
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiprotozoal activity of the constituents of Conyza filaginoides.
Year : 2001
Volume : 64
Issue : 5
First Page : 671
Last Page : 673
Authors : Calzada F, Cedillo-Rivera R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Conyza filaginoides led to the isolation of three new flavonol caffeoyl glycosides, namely, kaempferol 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (1), isorhamnetin 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (2), and quercetin 3-O-(6' '-O-E-caffeoyl)-beta-D-glucopyranoside (3). In addition, seven known compounds, erythrodiol (4), beta-caryophyllene-4,5-alpha-oxide (5), astragalin (6), isoquercitrin (7), nicotiflorin (8), narcissin (9), and rutin (10), were obtained. The structures of the new isolates were elucidated by spectroscopic and chemical methods. Compounds were also assessed for antiamoebic and antigiardial activities, but none was significantly active compared to the standard drugs evaluated.
Antifungal activity against Giardia intestinalis ATCC 30888 after 48 hrs by XTT assay
|
Giardia intestinalis
|
0.1
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antigiardial activity of isoflavones from Dalbergia frutescens bark.
Year : 2000
Volume : 63
Issue : 10
First Page : 1414
Last Page : 1416
Authors : Khan IA, Avery MA, Burandt CL, Goins DK, Mikell JR, Nash TE, Azadegan A, Walker LA.
Abstract : Several isoflavones [formononetin (1), castanin (5), odoratin (6), glycitein (7), pseudobaptogenin (8), fujikinetin (9), and cuneatin (10)] were isolated from Dalbergia frutescens, and their antiprotozoal activities were determined against Giardia intestinalis. Among these compounds, formononetin (1) was the most potent antigiardial agent, with an IC(50) value of 30 ng/mL (approximately 0.1 microM), as compared to the value for metronidazole, the current drug of choice, of 100 ng/mL (approximately 0.6 microM). Three isoflavones closely related to formononetin [daidzein (2), biochanin A (3) and genistein (4)] were also evaluated, but they were at least 100 times less active than 1. Formononetin (1) may thus be an interesting lead for development of new antigiardial agents or as a probe for a new mechanistic target.
Antiprotozoal activity against axenically grown trophozoites of Giardia lamblia IMSS:0989:1 after 48 hrs by MTT method
|
Giardia intestinalis
|
0.21
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Geranins A and B, new antiprotozoal A-type proanthocyanidins from Geranium niveum.
Year : 1999
Volume : 62
Issue : 5
First Page : 705
Last Page : 709
Authors : Calzada F, Cerda-García-Rojas CM, Meckes M, Cedillo-Rivera R, Bye R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Geranium niveum led to the isolation of two new A-type proanthocyanidins, epi-afzelechin-(4beta-->8, 2beta-->O-->7)-afzelechin (1) and epi-catechin-(4beta-->8, 2beta-->O-->7)-afzelechin (2). Compounds 1 and 2 were given the trivial names of geranins A and B, respectively. In addition, five known compounds, mahuannin B (3), reynoutrin (4), hyperin (5), methyl gallate (6), and 3-beta-caffeoyl-12-oleanen-28-oic acid (7), were obtained. The structures of the new proanthocyanidins were elucidated by spectroscopic and chemical methods as well as CD measurements. Compounds 1, 2, and 4-7 were tested against axenically grown trophozoites of Giardia lamblia and Entamoeba histolytica.
Antiprotozoal activity against axenically grown trophozoites of Entamoeba histolytica HM1-IMSS after 48 hrs by MTT method
|
Entamoeba histolytica
|
0.04
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Geranins A and B, new antiprotozoal A-type proanthocyanidins from Geranium niveum.
Year : 1999
Volume : 62
Issue : 5
First Page : 705
Last Page : 709
Authors : Calzada F, Cerda-García-Rojas CM, Meckes M, Cedillo-Rivera R, Bye R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Geranium niveum led to the isolation of two new A-type proanthocyanidins, epi-afzelechin-(4beta-->8, 2beta-->O-->7)-afzelechin (1) and epi-catechin-(4beta-->8, 2beta-->O-->7)-afzelechin (2). Compounds 1 and 2 were given the trivial names of geranins A and B, respectively. In addition, five known compounds, mahuannin B (3), reynoutrin (4), hyperin (5), methyl gallate (6), and 3-beta-caffeoyl-12-oleanen-28-oic acid (7), were obtained. The structures of the new proanthocyanidins were elucidated by spectroscopic and chemical methods as well as CD measurements. Compounds 1, 2, and 4-7 were tested against axenically grown trophozoites of Giardia lamblia and Entamoeba histolytica.
Antiprotozoal activity against Trichomonas vaginalis GT3 trophozoites after 48 hrs
|
Trichomonas vaginalis
|
236.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis and antiprotozoal activity of novel 1-methylbenzimidazole derivatives.
Year : 2009
Volume : 17
Issue : 4
First Page : 1724
Last Page : 1730
Authors : Valdez-Padilla D, Rodríguez-Morales S, Hernández-Campos A, Hernández-Luis F, Yépez-Mulia L, Tapia-Contreras A, Castillo R.
Abstract : In this paper are reported the synthesis and antiprotozoal activity in vitro of 24 1-methylbenzimidazole derivatives (13-36) substituted at position 2 with aminocarbonyl, N-methylaminocarbonyl, N,N-dimethylaminocarbonyl, ethoxycarbonyl, 1-hydroxyethyl and acetyl groups, some of them with chlorine atoms at the benzenoid ring. Compounds 13-36 were more active than metronidazole, the choice drug against Giardia intestinalis and most of them against Trichomonas vaginalis. The most active group of compounds for both parasites was that with a 2-ethoxycarbonyl group (16, 22, 28, 34), independently of the substitution pattern at the benzenoid ring.
Antiparasitic activity against Trichomonas vaginalis GT3 trophozoites after 48 hrs by Hill culture method
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles.
Year : 2009
Volume : 44
Issue : 7
First Page : 2975
Last Page : 2984
Authors : Hernández-Núñez E, Tlahuext H, Moo-Puc R, Torres-Gómez H, Reyes-Martínez R, Cedillo-Rivera R, Nava-Zuazo C, Navarrete-Vazquez G.
Abstract : Two new series of imidazole derivatives (acetamides: 1-8 and sulfonamides: 9-15) were synthesized using a short synthetic route. Compound 1 as well as the intermediate 16g were characterized by X-ray crystallography. Imidazole derivatives 1-15 were tested in vitro against three unicellular parasites (Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica) in comparison with benznidazole (Bzn) and metronidazole. Compound 1 [N-benzyl-2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetamide] was 2 times more active than Bzn against T. vaginalis and G. intestinalis and it was as active as Bzn against E. histolytica. Sulfonamides showed selective toxicity against E. histolytica over the other parasites. Toxicity assay showed that all compounds are non-cytotoxic against MDCK cell line. The results revealed that compounds 1-15 have antiparasitic bioactivity in the micromolar range against the parasites tested, and could be considered as benznidazole bioisosteres.
Antiamnesic activity against Entamoeba histolytica HM-1:IMSS trophozoites after 48 hrs by Hill culture method
|
Entamoeba histolytica HM-1:IMSS
|
770.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles.
Year : 2009
Volume : 44
Issue : 7
First Page : 2975
Last Page : 2984
Authors : Hernández-Núñez E, Tlahuext H, Moo-Puc R, Torres-Gómez H, Reyes-Martínez R, Cedillo-Rivera R, Nava-Zuazo C, Navarrete-Vazquez G.
Abstract : Two new series of imidazole derivatives (acetamides: 1-8 and sulfonamides: 9-15) were synthesized using a short synthetic route. Compound 1 as well as the intermediate 16g were characterized by X-ray crystallography. Imidazole derivatives 1-15 were tested in vitro against three unicellular parasites (Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica) in comparison with benznidazole (Bzn) and metronidazole. Compound 1 [N-benzyl-2-(2-methyl-4-nitro-1H-imidazol-1-yl)acetamide] was 2 times more active than Bzn against T. vaginalis and G. intestinalis and it was as active as Bzn against E. histolytica. Sulfonamides showed selective toxicity against E. histolytica over the other parasites. Toxicity assay showed that all compounds are non-cytotoxic against MDCK cell line. The results revealed that compounds 1-15 have antiparasitic bioactivity in the micromolar range against the parasites tested, and could be considered as benznidazole bioisosteres.
Antigiardial activity against Giardia lamblia WB (ATCC 30957) trophozoites after 24 hrs by trypan blue assay
|
Giardia intestinalis
|
2.88
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Solution-phase parallel synthesis of substituted chalcones and their antiparasitary activity against Giardia lamblia.
Year : 2009
Volume : 17
Issue : 18
First Page : 6780
Last Page : 6785
Authors : Montes-Avila J, Díaz-Camacho SP, Sicairos-Félix J, Delgado-Vargas F, Rivero IA.
Abstract : A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) values were 12.72, 15.05 and 15.31 microg/mL, respectively; these are potential leads for the development of antigiardial compounds.
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS after 48 hrs
|
Entamoeba histolytica HM-1:IMSS
|
350.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives against some protozoa and Trichinella spiralis.
Year : 2010
Volume : 45
Issue : 7
First Page : 3135
Last Page : 3141
Authors : Hernández-Luis F, Hernández-Campos A, Castillo R, Navarrete-Vázquez G, Soria-Arteche O, Hernández-Hernández M, Yépez-Mulia L.
Abstract : A series of 2-(trifluoromethyl)-1H-benzimidazole derivatives (1a-1i) were synthesized via Phillips cyclocondensation of a substituted 1,2-phenylenediamine and trifluoroacetic acid. The synthesized compounds were evaluated in vitro against various protozoan parasites: Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis and Leishmania mexicana, and they showed nanomolar activities against the first three protozoa tested. The compounds were also tested in vitro and in vivo against the nematode Trichinella spiralis. Compounds 1b, 1c and 1e had the most desirable in vitro antiparasitic profile against all parasites studied. In the in vivo model against T. spiralis, compounds 1b and 1e showed good activity against the adult phase at 75 mg/Kg. However, against the muscle larvae stage, only compound 1f exhibited in vivo antiparasitic efficacy.
Antiprotozoal activity against Trichomonas vaginalis G3 after 48 hrs
|
Trichomonas vaginalis G3
|
216.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and biological activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives against some protozoa and Trichinella spiralis.
Year : 2010
Volume : 45
Issue : 7
First Page : 3135
Last Page : 3141
Authors : Hernández-Luis F, Hernández-Campos A, Castillo R, Navarrete-Vázquez G, Soria-Arteche O, Hernández-Hernández M, Yépez-Mulia L.
Abstract : A series of 2-(trifluoromethyl)-1H-benzimidazole derivatives (1a-1i) were synthesized via Phillips cyclocondensation of a substituted 1,2-phenylenediamine and trifluoroacetic acid. The synthesized compounds were evaluated in vitro against various protozoan parasites: Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis and Leishmania mexicana, and they showed nanomolar activities against the first three protozoa tested. The compounds were also tested in vitro and in vivo against the nematode Trichinella spiralis. Compounds 1b, 1c and 1e had the most desirable in vitro antiparasitic profile against all parasites studied. In the in vivo model against T. spiralis, compounds 1b and 1e showed good activity against the adult phase at 75 mg/Kg. However, against the muscle larvae stage, only compound 1f exhibited in vivo antiparasitic efficacy.
Antiparasitic activity against Trichomonas vaginalis T1 after 24 hrs by hemocytometric analysis
|
Trichomonas vaginalis
|
720.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Preliminary studies of 3,4-dichloroaniline amides as antiparasitic agents: structure-activity analysis of a compound library in vitro against Trichomonas vaginalis.
Year : 2010
Volume : 20
Issue : 17
First Page : 5299
Last Page : 5301
Authors : Dornbush PJ, Cho C, Chang ES, Xu L, Russu WA, Wrischnik LA, Land KM.
Abstract : Trichomonas vaginalis, a human-infectious protozoan, can display resistance to treatment by metronidazole. A library of 3,4-dichloroaniline amides based on propanil, an herbicide, has been synthesized and screened to test susceptibility to these analogs. From this preliminary study, the most effective compound 15, inhibits growth of the organism by 66% and 69% on the two strains tested, T1 and G3, respectively.
Antiparasitic activity against Trichomonas vaginalis G3 after 24 hrs by hemocytometric analysis
|
Trichomonas vaginalis G3
|
770.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Preliminary studies of 3,4-dichloroaniline amides as antiparasitic agents: structure-activity analysis of a compound library in vitro against Trichomonas vaginalis.
Year : 2010
Volume : 20
Issue : 17
First Page : 5299
Last Page : 5301
Authors : Dornbush PJ, Cho C, Chang ES, Xu L, Russu WA, Wrischnik LA, Land KM.
Abstract : Trichomonas vaginalis, a human-infectious protozoan, can display resistance to treatment by metronidazole. A library of 3,4-dichloroaniline amides based on propanil, an herbicide, has been synthesized and screened to test susceptibility to these analogs. From this preliminary study, the most effective compound 15, inhibits growth of the organism by 66% and 69% on the two strains tested, T1 and G3, respectively.
Antimicrobial activity against Trichomonas vaginalis GT3 after 48 hrs
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.
Year : 2010
Volume : 18
Issue : 17
First Page : 6398
Last Page : 6403
Authors : Nava-Zuazo C, Estrada-Soto S, Estrada-Soto S, Guerrero-Alvarez J, León-Rivera I, Molina-Salinas GM, Said-Fernández S, Chan-Bacab MJ, Cedillo-Rivera R, Moo-Puc R, Mirón-López G, Navarrete-Vazquez G.
Abstract : We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.
Antimicrobial activity against Entamoeba histolytica HM-1:IMSS after 48 hrs
|
Entamoeba histolytica HM-1:IMSS
|
770.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.
Year : 2010
Volume : 18
Issue : 17
First Page : 6398
Last Page : 6403
Authors : Nava-Zuazo C, Estrada-Soto S, Estrada-Soto S, Guerrero-Alvarez J, León-Rivera I, Molina-Salinas GM, Said-Fernández S, Chan-Bacab MJ, Cedillo-Rivera R, Moo-Puc R, Mirón-López G, Navarrete-Vazquez G.
Abstract : We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.
Inhibition of Helicobacter pylori invasion into human AGS cells at 2.5 uM after 6 hrs
|
Helicobacter pylori
|
20.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification of 3',4',5'-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells.
Year : 2010
Volume : 20
Issue : 18
First Page : 5462
Last Page : 5465
Authors : Lai CH, Rao YK, Fang SH, Sing YT, Tzeng YM.
Abstract : Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8.
Inhibition of Helicobacter pylori-induced inflammation in human AGS cells assessed as reduction of IL-8 production at 10 uM by ELISA
|
Helicobacter pylori
|
81.9
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification of 3',4',5'-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells.
Year : 2010
Volume : 20
Issue : 18
First Page : 5462
Last Page : 5465
Authors : Lai CH, Rao YK, Fang SH, Sing YT, Tzeng YM.
Abstract : Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8.
Antitrypanosomal activity against Trichomonas vaginalis T1
|
Trichomonas vaginalis
|
720.0
nM
|
|
Antitrypanosomal activity against Trichomonas vaginalis T1
|
Trichomonas vaginalis
|
0.12
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : AdoHcy hydrolase of Trichomonas vaginalis: studies of the effects of 5'-modified adenosine analogues and related 6-N-cyclopropyl derivatives.
Year : 2010
Volume : 20
Issue : 24
First Page : 7466
Last Page : 7468
Authors : Dornbush PJ, Vazquez-Anaya G, Shokar A, Benson S, Rapp M, Wnuk SF, Wrischnik LA, Land KM.
Abstract : Trypanosoma brucei and Trichomonas vaginalis are both parasitic protozoans that are known to share many similar biochemical pathways. Aristeromycin, as well as 5'-iodovinyl and 5'-oxime analogues of adenosine, are potent inhibitors of AdoHcy hydrolase in T. brucei, an enzyme that catalyses the hydrolysis of AdoHcy to adenosine and L-homocysteine. To help determine the role of this enzyme in T. vaginalis, we have tested a library of 5'-modified adenosine derivatives, including 5'-deoxy-5'-(iodomethylene)-adenosine and related 6-N-cyclopropyl analogues. Our results indicate that these inhibitors are effective at inhibiting the growth of T. vaginalis, by as much as 95%.
Antimicrobial activity against Escherichia coli JM109 transformed with empty vector PQE30 after 16 hrs
|
Escherichia coli
|
25.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Year : 2009
Volume : 53
Issue : 2
First Page : 458
Last Page : 464
Authors : Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J.
Abstract : Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
Antimicrobial activity against Escherichia coli JM109 transformed with Entamoeba histolytica NTR1 after 16 hrs
|
Escherichia coli
|
7.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Year : 2009
Volume : 53
Issue : 2
First Page : 458
Last Page : 464
Authors : Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J.
Abstract : Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
Antimicrobial activity against Escherichia coli JM109 transformed with Entamoeba histolytica NTR2 after 16 hrs
|
Escherichia coli
|
8.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Year : 2009
Volume : 53
Issue : 2
First Page : 458
Last Page : 464
Authors : Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J.
Abstract : Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
Antimicrobial activity against Escherichia coli JM109 transformed with Entamoeba histolytica nim1 after 16 hrs
|
Escherichia coli
|
750.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Year : 2009
Volume : 53
Issue : 2
First Page : 458
Last Page : 464
Authors : Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J.
Abstract : Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
Antimicrobial activity against Escherichia coli JM109 transformed with Trichomonas vaginalis nim1 after 16 hrs
|
Escherichia coli
|
500.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).
Year : 2009
Volume : 53
Issue : 2
First Page : 458
Last Page : 464
Authors : Pal D, Banerjee S, Cui J, Schwartz A, Ghosh SK, Samuelson J.
Abstract : Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.
Antiprotozoan activity against Trichomonas vaginalis GT3 trophozoites after 48 hrs
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis of benzologues of Nitazoxanide and Tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity.
Year : 2011
Volume : 21
Issue : 10
First Page : 3168
Last Page : 3171
Authors : Navarrete-Vazquez G, Chávez-Silva F, Argotte-Ramos R, Rodríguez-Gutiérrez Mdel C, Chan-Bacab MJ, Cedillo-Rivera R, Moo-Puc R, Hernández-Nuñez E.
Abstract : We have synthesized two new benzologues of Nitazoxanide (NIT) and Tizoxanide (TIZ), using a short synthetic route. Both compounds were tested in vitro against six protozoa (Giardia intestinalis, Trichomonas vaginalis, Entamoeba histolytica, Plasmodium berghei, Leishmania mexicana and Trypanosoma cruzi). Compound 1 (benzologue of NIT) showed broad antiprotozoal effect against all parasites tested, showing IC(50)'s<5 μM. This compound was five-times more active than NIT, and 18-times more potent than metronidazole against G. intestinalis. It was 10-times more active than pentamidine against L. mexicana, and it was sevenfold more potent than benznidazole versus T. cruzi. This compound could be considered as a new broad spectrum antiprotozoal agent.
Antiprotozoan activity against Entamoeba histolytica HM1-IMSS trophozoites after 48 hrs
|
Entamoeba histolytica
|
770.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis of benzologues of Nitazoxanide and Tizoxanide: a comparative study of their in vitro broad-spectrum antiprotozoal activity.
Year : 2011
Volume : 21
Issue : 10
First Page : 3168
Last Page : 3171
Authors : Navarrete-Vazquez G, Chávez-Silva F, Argotte-Ramos R, Rodríguez-Gutiérrez Mdel C, Chan-Bacab MJ, Cedillo-Rivera R, Moo-Puc R, Hernández-Nuñez E.
Abstract : We have synthesized two new benzologues of Nitazoxanide (NIT) and Tizoxanide (TIZ), using a short synthetic route. Both compounds were tested in vitro against six protozoa (Giardia intestinalis, Trichomonas vaginalis, Entamoeba histolytica, Plasmodium berghei, Leishmania mexicana and Trypanosoma cruzi). Compound 1 (benzologue of NIT) showed broad antiprotozoal effect against all parasites tested, showing IC(50)'s<5 μM. This compound was five-times more active than NIT, and 18-times more potent than metronidazole against G. intestinalis. It was 10-times more active than pentamidine against L. mexicana, and it was sevenfold more potent than benznidazole versus T. cruzi. This compound could be considered as a new broad spectrum antiprotozoal agent.
Antiprotozoan activity against Trichomonas vaginalis GT3 trophozoites compound treated for 48 hrs measured after 48 hrs washout period
|
Trichomonas vaginalis
|
236.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiprotozoal activity of proton-pump inhibitors.
Year : 2011
Volume : 21
Issue : 24
First Page : 7351
Last Page : 7354
Authors : Pérez-Villanueva J, Romo-Mancillas A, Hernández-Campos A, Yépez-Mulia L, Hernández-Luis F, Castillo R.
Abstract : Parasitic diseases are still a major health problem in developing countries. In our effort to find new antiparasitic agents, in this Letter we report the in vitro antiprotozoal activity of omeprazole, lansoprazole, rabeprazole and pantoprazole against Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Molecular modeling studies were an important tool to highlight the potential antiprotozoal activity of these drugs. Experimental evaluations revealed a strong activity for all compounds tested. Rabeprazole and pantoprazole were the most active compounds, having IC(50) values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites.
Antiprotozoan activity against Entamoeba histolytica HM1-IMSS trophozoites compound treated for 48 hrs measured after 48 hrs washout period
|
Entamoeba histolytica
|
350.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiprotozoal activity of proton-pump inhibitors.
Year : 2011
Volume : 21
Issue : 24
First Page : 7351
Last Page : 7354
Authors : Pérez-Villanueva J, Romo-Mancillas A, Hernández-Campos A, Yépez-Mulia L, Hernández-Luis F, Castillo R.
Abstract : Parasitic diseases are still a major health problem in developing countries. In our effort to find new antiparasitic agents, in this Letter we report the in vitro antiprotozoal activity of omeprazole, lansoprazole, rabeprazole and pantoprazole against Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Molecular modeling studies were an important tool to highlight the potential antiprotozoal activity of these drugs. Experimental evaluations revealed a strong activity for all compounds tested. Rabeprazole and pantoprazole were the most active compounds, having IC(50) values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites.
Growth inhibition of Trichomonas vaginalis T1 after 24 hrs by hemocytometry
|
Trichomonas vaginalis
|
720.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine.
Year : 2012
Volume : 22
Issue : 12
First Page : 4203
Last Page : 4205
Authors : Shokar A, Au A, An SH, Tong E, Garza G, Zayas J, Wnuk SF, Land KM.
Abstract : In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.
Growth inhibition of mtronidazole-resistant Trichomonas vaginalis after 24 hrs by hemocytometry
|
Trichomonas vaginalis
|
210.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine.
Year : 2012
Volume : 22
Issue : 12
First Page : 4203
Last Page : 4205
Authors : Shokar A, Au A, An SH, Tong E, Garza G, Zayas J, Wnuk SF, Land KM.
Abstract : In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.
Inhibition of Helicobacter pylori invasion to human AGS cells at 20 ug/ml after 6 hrs by gentamicin assay relative to control
|
Helicobacter pylori
|
20.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells.
Year : 2012
Volume : 48
First Page : 244
Last Page : 254
Authors : Chang CS, Liu JF, Lin HJ, Lin CD, Tang CH, Lu DY, Sing YT, Chen LY, Kao MC, Kuo SC, Lai CH.
Abstract : Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.
Inhibition of Helicobacter pylori adhesion to human AGS cells at 20 ug/ml after 6 hrs by gentamicin assay relative to control
|
Helicobacter pylori
|
20.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and bioevaluation of novel 3,4,5-trimethoxybenzylbenzimidazole derivatives that inhibit Helicobacter pylori-induced pathogenesis in human gastric epithelial cells.
Year : 2012
Volume : 48
First Page : 244
Last Page : 254
Authors : Chang CS, Liu JF, Lin HJ, Lin CD, Tang CH, Lu DY, Sing YT, Chen LY, Kao MC, Kuo SC, Lai CH.
Abstract : Helicobacter pylori infection is associated with gastritis, peptic ulcer, and even gastric malignancy. H. pylori's antibiotic resistance is the major obstacle preventing its eradication. A series of 3,4,5-trimethoxybenzylbenzimidazole derivatives were synthesized and evaluated for their anti-H. pylori activity. The compound, 2-fluorophenyl-5-methyl-1-(3,4,5-trimethoxybenzyl)benzimidazole (FMTMB), was determined as the most potent in the inhibition of H. pylori growth and pathogenesis of host cells. An in vitro H. pylori infection model revealed that FMTMB inhibited H. pylori adhesion and invasion of gastric epithelial cells. Results from this study provide evidence that FMTMB is a potent therapeutic agent that exhibits both anti-H. pylori growth properties and anti-H. pylori-induced pathogenesis of cells.
Antibacterial activity against Trichomonas vaginalis G3 after 24 hrs by hemocytometry
|
Trichomonas vaginalis G3
|
720.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of 1H-1,2,3-triazole linked β-lactam-isatin bi-functional hybrids and preliminary analysis of in vitro activity against the protozoal parasite Trichomonas vaginalis.
Year : 2013
Volume : 63
First Page : 897
Last Page : 906
Authors : Raj R, Singh P, Haberkern NT, Faucher RM, Patel N, Land KM, Kumar V.
Abstract : Twenty-two different triazoles were prepared to examine the anti-Trichomonas vaginalis structure-activity relationships (SAR) within the β-lactam-isatin-triazole conjugate family. The compounds were synthesized by copper-catalyzed 'click chemistry.'In vitro activity against T. vaginalis was determined at 10 and 100 μM for each compound, with eighteen of the synthesized hybrids showing 100% growth inhibition at 100 μM. The compound 5i, with no cytotoxicity on cultured CHO-K1 cells, is considered a good compound for further analysis.
Antiprotozoal activity against trophozoite stage of Entamoeba histolytica HM-1:IMSS assessed as growth inhibition after 48 hrs by haemocytometric analysis
|
Entamoeba histolytica HM-1:IMSS
|
379.8
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiprotozoal activity of novel 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives.
Year : 2013
Volume : 23
Issue : 14
First Page : 4221
Last Page : 4224
Authors : Pérez-Villanueva J, Hernández-Campos A, Yépez-Mulia L, Méndez-Cuesta C, Méndez-Lucio O, Hernández-Luis F, Castillo R.
Abstract : A series of 19 new 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives was synthesized starting from the properly substituted 1,2-phenylendiamine. These compounds have hydrogen or methyl at position 1; while hydrogen, chlorine, ethoxy or methoxycarbonyl group is at position 5 and/or 6. The novel compounds were tested against protozoa Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Experimental evaluations revealed strong activity for all tested compounds, having IC50 values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites.
Antiprotozoal activity against trophozoite stage of Trichomonas vaginalis GT3 assessed as growth inhibition after 48 hrs by haemocytometric analysis
|
Trichomonas vaginalis
|
236.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antiprotozoal activity of novel 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives.
Year : 2013
Volume : 23
Issue : 14
First Page : 4221
Last Page : 4224
Authors : Pérez-Villanueva J, Hernández-Campos A, Yépez-Mulia L, Méndez-Cuesta C, Méndez-Lucio O, Hernández-Luis F, Castillo R.
Abstract : A series of 19 new 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives was synthesized starting from the properly substituted 1,2-phenylendiamine. These compounds have hydrogen or methyl at position 1; while hydrogen, chlorine, ethoxy or methoxycarbonyl group is at position 5 and/or 6. The novel compounds were tested against protozoa Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Experimental evaluations revealed strong activity for all tested compounds, having IC50 values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites.
Antiprotozoal activity against clinical isolates of Giardia lamblia IMSS:8901:1
|
Giardia intestinalis
|
0.21
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Hydroxyclerodanes from Salvia shannoni.
Year : 2013
Volume : 76
Issue : 10
First Page : 1970
Last Page : 1975
Authors : Bautista E, Toscano A, Calzada F, Díaz E, Yépez-Mulia L, Ortega A.
Abstract : Six new hydroxyclerodanes (1-6), named sepulturins A-F, and four known diterpenes were isolated from the leaves of Salvia shannoni. The structures of these compounds were established by extensive analysis of their NMR and MS spectroscopic data. The relative configurations of compounds 1 and 2 were determined by NOESY experiments and were confirmed by single-crystal X-ray diffraction studies. All of the isolated diterpenes possess tertiary OH groups. The structure of infuscatin (7), a clerodane previously isolated from S. infuscata, was revised. Cytotoxic, antiprotozoal, and anti-inflammatory activities of these compounds were evaluated.
Antiprotozoal activity against clinical isolates of Entamoeba histolytica HM-1:IMSS
|
Entamoeba histolytica HM-1:IMSS
|
0.04
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Hydroxyclerodanes from Salvia shannoni.
Year : 2013
Volume : 76
Issue : 10
First Page : 1970
Last Page : 1975
Authors : Bautista E, Toscano A, Calzada F, Díaz E, Yépez-Mulia L, Ortega A.
Abstract : Six new hydroxyclerodanes (1-6), named sepulturins A-F, and four known diterpenes were isolated from the leaves of Salvia shannoni. The structures of these compounds were established by extensive analysis of their NMR and MS spectroscopic data. The relative configurations of compounds 1 and 2 were determined by NOESY experiments and were confirmed by single-crystal X-ray diffraction studies. All of the isolated diterpenes possess tertiary OH groups. The structure of infuscatin (7), a clerodane previously isolated from S. infuscata, was revised. Cytotoxic, antiprotozoal, and anti-inflammatory activities of these compounds were evaluated.
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
102.59
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
98.27
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
Inhibition of COX-2 (unknown origin) using arachidonic acid as substrate assessed as formation of prostanoid products at 500 uM preincubated for 10 mins prior to substrate addition measured after 2 mins by Ellman's method relative to control
|
Homo sapiens
|
17.0
%
|
|
Journal : J. Med. Chem.
Title : Experimental confirmation of new drug-target interactions predicted by Drug Profile Matching.
Year : 2013
Volume : 56
Issue : 21
First Page : 8377
Last Page : 8388
Authors : Végner L, Peragovics Á, Tombor L, Jelinek B, Czobor P, Bender A, Simon Z, Málnási-Csizmadia A.
Abstract : We recently introduced Drug Profile Matching (DPM), a novel affinity fingerprinting-based in silico drug repositioning approach. DPM is able to quantitatively predict the complete effect profiles of compounds via probability scores. In the present work, in order to investigate the predictive power of DPM, three effect categories, namely, angiotensin-converting enzyme inhibitor, cyclooxygenase inhibitor, and dopamine agent, were selected and predictions were verified by literature analysis as well as experimentally. A total of 72% of the newly predicted and tested dopaminergic compounds were confirmed by tests on D1 and D2 expressing cell cultures. 33% and 23% of the ACE and COX inhibitory predictions were confirmed by in vitro tests, respectively. Dose-dependent inhibition curves were measured for seven drugs, and their inhibitory constants (Ki) were determined. Our study overall demonstrates that DPM is an effective approach to reveal novel drug-target pairs that may result in repositioning these drugs.
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS
|
Entamoeba histolytica HM-1:IMSS
|
230.0
nM
|
|
Journal : J. Nat. Prod.
Title : Structure, absolute configuration, and antidiarrheal activity of a thymol derivative from Ageratina cylindrica.
Year : 2014
Volume : 77
Issue : 2
First Page : 358
Last Page : 363
Authors : Bustos-Brito C, Sánchez-Castellanos M, Esquivel B, Calderón JS, Calzada F, Yepez-Mulia L, Hernández-Barragán A, Joseph-Nathan P, Cuevas G, Quijano L.
Abstract : The leaves of Ageratina cylindrica afforded a thymol derivative that was characterized by physical and spectroscopical methods as (8S)-8,9-epoxy-6-hydroxy-l0-benzoyloxy-7-oxothymol isobutyrate (1). The absolute configuration of 1 was established as 8S by vibrational circular dichroism spectroscopy in combination with density functional theory calculations and by evaluation of the Flack and Hooft X-ray parameters. Compound 1 showed weak antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites and a high inhibitory effect on hyperpropulsive movement of the small intestine in rats.
Antimicrobial activity against Trichomonas vaginalis GT3 incubated for 48 hrs followed by compound washout measured after 48 hrs
|
Trichomonas vaginalis
|
316.23
nM
|
|
Antimicrobial activity against Trichomonas vaginalis GT3 incubated for 48 hrs followed by compound washout measured after 48 hrs
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : 2-acylamino-5-nitro-1,3-thiazoles: preparation and in vitro bioevaluation against four neglected protozoan parasites.
Year : 2014
Volume : 22
Issue : 5
First Page : 1626
Last Page : 1633
Authors : Nava-Zuazo C, Chávez-Silva F, Moo-Puc R, Chan-Bacab MJ, Ortega-Morales BO, Moreno-Díaz H, Díaz-Coutiño D, Hernández-Núñez E, Navarrete-Vázquez G.
Abstract : The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50=10nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound.
Antiprotozoal activity against trophozoite stage of Trichomonas vaginalis GT3 assessed as growth inhibition
|
Trichomonas vaginalis
|
0.037
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis.
Year : 2014
Volume : 22
Issue : 4
First Page : 1370
Last Page : 1376
Authors : Cano PA, Islas-Jácome A, González-Marrero J, Yépez-Mulia L, Calzada F, Gámez-Montaño R.
Abstract : The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.
Antiprotozoal activity against trophozoite stage of Giardia lamblia IMSS:8909:1 assessed as growth inhibition after 48 hrs
|
Giardia intestinalis
|
1.22
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis.
Year : 2014
Volume : 22
Issue : 4
First Page : 1370
Last Page : 1376
Authors : Cano PA, Islas-Jácome A, González-Marrero J, Yépez-Mulia L, Calzada F, Gámez-Montaño R.
Abstract : The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.
Antiprotozoal activity against trophozoite stage of Entamoeba histolytica HM-1:IMSS assessed as growth inhibition after 48 hrs
|
Entamoeba histolytica HM-1:IMSS
|
0.23
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of 3-tetrazolylmethyl-4H-chromen-4-ones via Ugi-azide and biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis.
Year : 2014
Volume : 22
Issue : 4
First Page : 1370
Last Page : 1376
Authors : Cano PA, Islas-Jácome A, González-Marrero J, Yépez-Mulia L, Calzada F, Gámez-Montaño R.
Abstract : The synthesis of novel 3-tetrazolylmethyl-4H-chromen-4-ones via an Ugi-azide multicomponent reaction and their biological evaluation against Entamoeba histolytica, Giardia lamblia and Trichomona vaginalis are described. Reported yields are moderate to good and biological results show that these compounds could be considered as candidates to anti-parasitic drugs, especially against G. lamblia.
Antimicrobial activity against Trichomonas vaginalis G3 assessed as growth inhibition after 24 hrs by hemocytometry
|
Trichomonas vaginalis G3
|
720.0
nM
|
|
Journal : MedChemComm
Title : Design and synthesis of -amino alcohol based -lactamisatin chimeras and preliminary analysis of in vitro activity against the protozoal pathogen Trichomonas vaginalis
Year : 2013
Volume : 4
Issue : 6
First Page : 1018
Last Page : 1024
Authors : Nisha, Mehra V, Hopper M, Patel N, Hall D, Wrischnik LA, Land KM, Kumar V
Antiprotozoal activity against Giardia lamblia assessed as growth inhibition
|
Giardia intestinalis
|
580.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Exploring in vitro and in vivo Hsp90 inhibitors activity against human protozoan parasites.
Year : 2015
Volume : 25
Issue : 3
First Page : 462
Last Page : 465
Authors : Giannini G, Battistuzzi G.
Abstract : A set of compounds, previously selected as potent Hsp90α inhibitors, has been studied on a panel of human parasites. 5-Aryl-3,4-isoxazolediamide derivatives (1) were active against two protozoa, Trypanosoma brucei rhodesiense and Plasmodium falciparum, with a good tolerability toward cytotoxicity on non-malignant L6 rat myoblast cell line, unlike the 1,5-diaryl,4-carboxamides-1,2,3-triazole derivatives (2) which, while showing a single-digit nM range activity against the same protozoa, were also highly cytotoxic on L6 cells. In a subsequent in vivo study, two isoxazolediamide derivatives, 1a and 1b, were very efficacious on the sleeping sickness-causing agent with a clear parasitaemia during treatment. These data, however, showed that not all protozoa are sensitive to Hsp90 inhibitors, as well as not all Hsp90 inhibitors are equally active on parasites.
Antiprotozoan activity against Giardia lamblia G1
|
Giardia intestinalis
|
580.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite.
Year : 2015
Volume : 25
Issue : 3
First Page : 459
Last Page : 461
Authors : Giannini G, Battistuzzi G, Vignola D.
Abstract : Recent studies have highlighted a key role in regulating gene transcription, in both eukaryotes and prokaryotes, by enzymes that control the acetylation and deacetylation of histones. In particular, inhibitors of histone deacetylases (HDAC-Is) have been shown effective in controlling the development of many parasites, such as the plasmodium of malaria. Here we report the results of a study aimed at evaluating antiparasitic effect of two classes of HDAC-Is bearing different zinc binding group (hydroxamic acid vs thiol). The study showed that only the hydroxamic acid based HDAC inhibitors were active, with Plasmodium falciparum being the most sensitive parasite, having from low double-digit to single-digit nanomolar range in vitro activities. Among three derivatives evaluated also in vivo, ST8086AA1 (8) effectively inhibited 88% of the development of Plasmodium falciparum.
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS trophozoites assessed as growth inhibition compound treated for 48 hrs measured 48 hrs post wash-out by MTT assay
|
Entamoeba histolytica HM-1:IMSS
|
0.04
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiprotozoal activity of 8-acyl and 8-alkyl incomptine A analogs.
Year : 2014
Volume : 24
Issue : 15
First Page : 3260
Last Page : 3262
Authors : Bautista E, Calzada F, López-Huerta FA, Yépez-Mulia L, Ortega A.
Abstract : The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.
Antiprotozoal activity against Giardia lamblia IMSS: 8909:1 trophozoites assessed as growth inhibition compound treated for 48 hrs measured 48 hrs post wash-out by MTT assay
|
Giardia intestinalis
|
0.21
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiprotozoal activity of 8-acyl and 8-alkyl incomptine A analogs.
Year : 2014
Volume : 24
Issue : 15
First Page : 3260
Last Page : 3262
Authors : Bautista E, Calzada F, López-Huerta FA, Yépez-Mulia L, Ortega A.
Abstract : The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.
Trichomonicidal activity against Trichomonas vaginalis GT3 compound treated for 48 hrs followed by incubation for 48 hrs in compound-free medium by cell counting
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis.
Year : 2015
Volume : 23
Issue : 9
First Page : 2204
Last Page : 2210
Authors : Navarrete-Vázquez G, Chávez-Silva F, Colín-Lozano B, Estrada-Soto S, Hidalgo-Figueroa S, Guerrero-Álvarez J, Méndez ST, Reyes-Vivas H, Oria-Hernández J, Canul-Canché J, Ortiz-Andrade R, Moo-Puc R.
Abstract : We synthesized four 5-nitrothiazole (1-4) and four 6-nitrobenzothiazole acetamides (5-8) using an easy two step synthetic route. All compounds were tested in vitro against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis, showing excellent antiprotozoal effects. IC₅₀'s of the most potent compounds range from nanomolar to low micromolar order, being more active than their drugs of choice. Compound 1 (IC₅₀=122 nM), was 44-times more active than Metronidazole, and 10-fold more effective than Nitazoxanide against G. intestinalis and showed good trichomonicidal activity (IC₅₀=2.24 μM). This compound did not display in vitro cytotoxicity against VERO cells. The in vitro inhibitory effect of compounds 1-8 and Nitazoxanide against G. intestinalis fructose-1,6-biphosphate aldolase (GiFBPA) was evaluated as potential drug target, showing a clear inhibitory effect over the enzyme activity. Molecular docking of compounds 1, 4 and Nitazoxanide into the ligand binding pocket of GiFBPA, revealed contacts with the active site residues of the enzyme. Ligand efficiency metrics of 1 revealed optimal combinations of physicochemical and antiprotozoal properties, better than Nitazoxanide.
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg indomethacin mol equivalent, ip administered 1 hr prior to carrageenan challenge measured at 1 hr relative to control
|
Rattus norvegicus
|
66.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Year : 2015
Volume : 25
Issue : 11
First Page : 2314
Last Page : 2320
Authors : Naumov RN, Panda SS, Girgis AS, George RF, Farhat M, Katritzky AR.
Abstract : Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg indomethacin mol equivalent, ip administered 1 hr prior to carrageenan challenge measured at 2 hrs relative to control
|
Rattus norvegicus
|
66.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Year : 2015
Volume : 25
Issue : 11
First Page : 2314
Last Page : 2320
Authors : Naumov RN, Panda SS, Girgis AS, George RF, Farhat M, Katritzky AR.
Abstract : Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg indomethacin mol equivalent, ip administered 1 hr prior to carrageenan challenge measured at 3 hrs relative to control
|
Rattus norvegicus
|
60.8
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Year : 2015
Volume : 25
Issue : 11
First Page : 2314
Last Page : 2320
Authors : Naumov RN, Panda SS, Girgis AS, George RF, Farhat M, Katritzky AR.
Abstract : Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg indomethacin mol equivalent, ip administered 1 hr prior to carrageenan challenge measured at 4 hrs relative to control
|
Rattus norvegicus
|
58.9
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Year : 2015
Volume : 25
Issue : 11
First Page : 2314
Last Page : 2320
Authors : Naumov RN, Panda SS, Girgis AS, George RF, Farhat M, Katritzky AR.
Abstract : Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.
Antiinflammatory activity in Wistar rat assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg indomethacin mol equivalent, ip administered 1 hr prior to carrageenan challenge measured at 24 hrs relative to control
|
Rattus norvegicus
|
0.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates.
Year : 2015
Volume : 25
Issue : 11
First Page : 2314
Last Page : 2320
Authors : Naumov RN, Panda SS, Girgis AS, George RF, Farhat M, Katritzky AR.
Abstract : Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 300 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 150 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 75 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 37.5 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
99.37
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 18.75 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
95.98
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis JH31A#4 trophozite assessed as inhibition of parasite growth at 9.37 uM after 24 hrs by resazurin redox dye based fluorimetric microtiter method
|
Trichomonas vaginalis
|
82.69
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Trichomonicidal activity against Trichomonas vaginalis C-1:NIH trophozoites infected in NMRI mouse assessed as reduction of pathogenicity at 25 mg/kg/day, po administered for 7 days from day 3 to day 10 post-infection measured at day 15 post-infection
|
Trichomonas vaginalis
|
93.96
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents.
Year : 2015
Volume : 94
First Page : 276
Last Page : 283
Authors : Ibáñez-Escribano A, Reviriego F, Nogal-Ruiz JJ, Meneses-Marcel A, Gómez-Barrio A, Escario JA, Arán VJ.
Abstract : Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's "rule of five". 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS
|
Entamoeba histolytica HM-1:IMSS
|
230.0
nM
|
|
Journal : J. Nat. Prod.
Title : ent-Kaurene Glycosides from Ageratina cylindrica.
Year : 2015
Volume : 78
Issue : 11
First Page : 2580
Last Page : 2587
Authors : Bustos-Brito C, Sánchez-Castellanos M, Esquivel B, Calderón JS, Calzada F, Yépez-Mulia L, Joseph-Nathan P, Cuevas G, Quijano L.
Abstract : The aqueous extract of the leaves of Ageratina cylindrica afforded six new ent-kaurenoic acid glycosides together with the known diterpenoid paniculoside V, the flavonoid astragalin, chlorogenic acid, and L-chiro-inositol. The structures were elucidated mainly by NMR and MS methods, and the absolute configuration was established by vibrational circular dichroism spectroscopy. The new compounds showed moderate antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites.
Antiparasitic activity against metronidazole sensitive Trichomonas vaginalis F1623 trophozoites after 24 to 48 hrs under anaerobic conditions by Celltiter-Glo assay
|
Trichomonas vaginalis
|
800.0
nM
|
|
Antiparasitic activity against metronidazole sensitive Trichomonas vaginalis F1623 trophozoites after 24 to 48 hrs under anaerobic conditions by Celltiter-Glo assay
|
Trichomonas vaginalis
|
794.33
nM
|
|
Journal : Eur J Med Chem
Title : Nitroimidazole carboxamides as antiparasitic agents targeting Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis.
Year : 2016
Volume : 120
First Page : 353
Last Page : 362
Authors : Jarrad AM, Debnath A, Miyamoto Y, Hansford KA, Pelingon R, Butler MS, Bains T, Karoli T, Blaskovich MA, Eckmann L, Cooper MA.
Abstract : Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives. Using this approach, derivatisation of the nitroimidazole carboxamide scaffold provided improved antiparasitic agents. Thirty-three novel nitroimidazole carboxamides were synthesised and evaluated for activity against G. lamblia and E. histolytica. Several of the new compounds exhibited potent activity against G. lamblia strains, including metronidazole-resistant strains of G. lamblia (EC50 = 0.1-2.5 μM cf. metronidazole EC50 = 6.1-18 μM). Other compounds showed improved activity against E. histolytica (EC50 = 1.7-5.1 μM cf. metronidazole EC50 = 5.0 μM), potent activity against Trichomonas vaginalis (EC50 = 0.6-1.4 μM cf. metronidazole EC50 = 0.8 μM) and moderate activity against the intestinal bacterial pathogen Clostridium difficile (0.5-2 μg/mL, cf. metronidazole = 0.5 μg/mL). The new compounds had low toxicity against mammalian kidney and liver cells (CC50 > 100 μM), and selected antiparasitic hits were assessed for human plasma protein binding and metabolic stability in liver microsomes to demonstrate their therapeutic potential.
Antiprotozoal activity against Trichomonas vaginalis GT3 trophozoites incubated for 48 hrs
|
Trichomonas vaginalis
|
290.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Synthesis, in vitro and in vivo giardicidal activity of nitrothiazole-NSAID chimeras displaying broad antiprotozoal spectrum.
Year : 2017
Volume : 27
Issue : 15
First Page : 3490
Last Page : 3494
Authors : Colín-Lozano B, León-Rivera I, Chan-Bacab MJ, Ortega-Morales BO, Moo-Puc R, López-Guerrero V, Hernández-Núñez E, Argüello-Garcia R, Scior T, Barbosa-Cabrera E, Navarrete-Vázquez G.
Abstract : We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis. In particular, compound 4 (an indomethacin hybrid) was one of the most potent of the series, inhibiting G. intestinalis growth in vitro with an IC50 of 0.145μM. Compound 4 was 38-times more potent than metronidazole and 8-times more active than nitazoxanide. The in vivo giardicidal effect of 4 was evaluated in a CD-1 mouse model obtaining a median effective dose of 1.709μg/kg (3.53nmol/kg), a 321-fold and 1015-fold increase in effectiveness after intragastric administration over metronidazole and nitazoxanide, respectively. Compounds 1 and 3 (hybrids of ibuprofen and clofibric acid), showed potent giardicidal activities in the in vitro as well as in the in vivo assays after oral administration. Therefore, compounds 1-5 constitute promising drug candidates for further testing in experimental chemotherapy against giardiasis, trichomoniasis, leishmaniasis and even trypanosomiasis infections.
Antiparasitic activity against trophozoite stage of Trichomonas vaginalis CNCD 147 after 48 hrs
|
Trichomonas vaginalis
|
236.0
nM
|
|
Journal : Eur J Med Chem
Title : Synthesis, antiprotozoal activity, and chemoinformatic analysis of 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives: Identification of new selective giardicidal and trichomonicidal compounds.
Year : 2017
Volume : 137
First Page : 211
Last Page : 220
Authors : Flores-Carrillo P, Velázquez-López JM, Aguayo-Ortiz R, Hernández-Campos A, Trejo-Soto PJ, Yépez-Mulia L, Castillo R.
Abstract : A series of twelve new 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives (1-12) were synthesized and their antiparasitic activity was tested in vitro against Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica. Experimental evaluations showed IC50 values within the nanomolar range for all tested compounds, some showing higher activity than metronidazole and albendazole. A chemoinformatic study was used to compare the structure-activity relationship of the synthesized carboxamides with those of 91 previously studied benzimidazoles, and with some Nitazoxanide-N-methylbenzimidazole hybrids recently synthetized by our group. Compounds 1 and 3 were identified as prominent selective compounds against T. vaginalis and G. intestinalis, respectively, while compound 4 was found to be of broad spectrum against the three protozoans.
Antiparasitic activity against trophozoite stage of Entamoeba histolytica HM-1:IMSS after 48 hrs
|
Entamoeba histolytica HM-1:IMSS
|
379.8
nM
|
|
Journal : Eur J Med Chem
Title : Synthesis, antiprotozoal activity, and chemoinformatic analysis of 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives: Identification of new selective giardicidal and trichomonicidal compounds.
Year : 2017
Volume : 137
First Page : 211
Last Page : 220
Authors : Flores-Carrillo P, Velázquez-López JM, Aguayo-Ortiz R, Hernández-Campos A, Trejo-Soto PJ, Yépez-Mulia L, Castillo R.
Abstract : A series of twelve new 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives (1-12) were synthesized and their antiparasitic activity was tested in vitro against Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica. Experimental evaluations showed IC50 values within the nanomolar range for all tested compounds, some showing higher activity than metronidazole and albendazole. A chemoinformatic study was used to compare the structure-activity relationship of the synthesized carboxamides with those of 91 previously studied benzimidazoles, and with some Nitazoxanide-N-methylbenzimidazole hybrids recently synthetized by our group. Compounds 1 and 3 were identified as prominent selective compounds against T. vaginalis and G. intestinalis, respectively, while compound 4 was found to be of broad spectrum against the three protozoans.
Inhibition of Bacillus pasteurii urease using urea as substrate measured after 20 mins by phenol reagent based assay relative to control
|
Sporosarcina pasteurii
|
13.0
%
|
|
Journal : Eur J Med Chem
Title : Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity relationship, antibacterial and urease inhibition activity.
Year : 2018
Volume : 145
First Page : 140
Last Page : 153
Authors : Ullah A, Iftikhar F, Arfan M, Batool Kazmi ST, Anjum MN, Haq IU, Ayaz M, Farooq S, Rashid U.
Abstract : Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 μM (2 μg/mL) for S. aureus and 1.1 μM (0.66 μg/mL) for E. coli. The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC50 = 6.23 ± 0.09 μM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP) were carried out.
Antiparasitic activity against Trichomonas vaginalis assessed as parasite growth inhibition after 24 hrs by hemacytometer
|
Trichomonas vaginalis
|
720.0
nM
|
|
Journal : MedChemComm
Title : Design, Synthesis and Preliminary Antimicrobial Evaluation of <i>N</i>-Alkyl Chain Tethered C-5 Functionalized Bis-Isatins.
Year : 2017
Volume : 8
Issue : 10
First Page : 1982
Last Page : 1992
Authors : Singh A, Nisha, Bains T, Hahn HJ, Liu N, Tam C, Cheng LW, Kim J, Debnath A, Land KM, Kumar V.
Abstract : A series of <i>N</i>-alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound <b>4t</b>, with an optimal combination of bromo-substituent at the C-5 position of isatin ring along with propyl chain linker being most active among the synthesized series exhibiting an IC<sub>50</sub> value of 3.72 μM against <i>Trichomonas vaginalis</i> while <b>4j</b> exhibited an IC<sub>50</sub> value of 14.8 μM against <i>Naegleria fowleri</i>, more effective than the standard drug Miltefosine. The compound <b>3f</b> with an octyl spacer length was the most potent among the series against <i>Giardia lamblia</i> with an IC<sub>50</sub> of 18.4 μM while <b>3d</b> exhibited an IC<sub>50</sub> of 23 μM against <i>Entamoeba histolytica</i>. This library was also screened against the fungal pathogen <i>Aspergillus parasiticus</i>. A number of the compounds demonstrated potency against this fungus, illustrating a possible broad-spectrum activity. Furthermore, an evaluation of these synthesized compounds against a panel of normal flora bacteria revealed them to be non-cytotoxic, demonstrating the selectivity of these compounds. This observation, in combination with previous studies that isatin is non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
17.23
%
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
2.82
%
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
13.91
%
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
12.01
%
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
26.53
%
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
1.89
%
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
-8.47
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
3.8
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
Cytotoxicity against human HT-29 cells after 24 hrs by MTT assay
|
Homo sapiens
|
278.08
ug.mL-1
|
|
Journal : Bioorg Med Chem
Title : Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.
Year : 2019
Volume : 27
Issue : 2
First Page : 305
Last Page : 314
Authors : Faghih-Mirzaei E, Sabouri S, Zeidabadinejad L, AbdolahRamazani S, Abaszadeh M, Khodadadi A, Shamsadinipour M, Jafari M, Pirhadi S.
Abstract : A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.
Cytotoxicity against human A549 cells after 24 hrs by MTT assay
|
Homo sapiens
|
223.78
ug.mL-1
|
|
Journal : Bioorg Med Chem
Title : Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.
Year : 2019
Volume : 27
Issue : 2
First Page : 305
Last Page : 314
Authors : Faghih-Mirzaei E, Sabouri S, Zeidabadinejad L, AbdolahRamazani S, Abaszadeh M, Khodadadi A, Shamsadinipour M, Jafari M, Pirhadi S.
Abstract : A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.
Cytotoxicity against human MCF7 cells after 24 hrs by MTT assay
|
Homo sapiens
|
347.96
ug.mL-1
|
|
Journal : Bioorg Med Chem
Title : Metronidazole aryloxy, carboxy and azole derivatives: Synthesis, anti-tumor activity, QSAR, molecular docking and dynamics studies.
Year : 2019
Volume : 27
Issue : 2
First Page : 305
Last Page : 314
Authors : Faghih-Mirzaei E, Sabouri S, Zeidabadinejad L, AbdolahRamazani S, Abaszadeh M, Khodadadi A, Shamsadinipour M, Jafari M, Pirhadi S.
Abstract : A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.
Antiparasitic activity against Entamoeba histolytica HM1-IMSS trophozoites assessed as inhibition of parasitic growth treated for 48 hrs followed by compound washout and measured after 48 hrs by MTT/PMS dye based colorimetric method
|
Entamoeba histolytica
|
200.0
nM
|
|
Journal : J Nat Prod
Title : Structure and Absolute Configuration of Abietane Diterpenoids from Salvia clinopodioides: Antioxidant, Antiprotozoal, and Antipropulsive Activities.
Year : 2019
Volume : 82
Issue : 5
First Page : 1207
Last Page : 1216
Authors : Bustos-Brito C, Joseph-Nathan P, Burgueño-Tapia E, Martínez-Otero D, Nieto-Camacho A, Calzada F, Yépez-Mulia L, Esquivel B, Quijano L.
Abstract : The aerial parts of Salvia clinopodioides afforded abietanes 1a, 2a, and 3 (clinopodiolides A-C), two of which possess an unusual lactol moiety at C-19-C-20, together with an icetexane named clinopodiolide D (4a). Their structures were established by spectroscopic means, mainly <sup>1</sup>H and <sup>13</sup>C NMR, including 1D and 2D homo- and heteronuclear experiments. The antioxidant, antiprotozoal, and antidiarrheal effects of the isolates were evaluated. Compounds 2a and 3 showed better effects than α-tocopherol in the inhibition of lipid peroxidation with IC<sub>50</sub> (μM) = 5.9 ± 0.1 and 2.7 ± 0.2, respectively, and moderate activity in the DPPH assay. All tested compounds showed moderate antiamoebic and antigiardial activity, as well as a good antipropulsive effect.
Antileishmanial activity against Leishmania donovani MHOM/IN/80/Dd8 promastigotes harboring luciferase reporter gene at 50 uM after 48 hrs by Steady-Glo luminescence assay relative to control
|
Leishmania donovani
|
62.2
%
|
|
Journal : J Med Chem
Title : Synthesis, Biological Evaluation, Structure-Activity Relationship, and Mechanism of Action Studies of Quinoline-Metronidazole Derivatives Against Experimental Visceral Leishmaniasis.
Year : 2019
Volume : 62
Issue : 11
First Page : 5655
Last Page : 5671
Authors : Upadhyay A, Chandrakar P, Gupta S, Parmar N, Singh SK, Rashid M, Kushwaha P, Wahajuddin M, Sashidhara KV, Kar S.
Abstract : In our efforts to identify novel chemical scaffolds for the development of antileishmanial agents, a series of quinoline-metronidazole hybrid compounds was synthesized and tested against the murine model of visceral leishmaniasis. Among all synthesized derivatives, 15b and 15i showed significant antileishmanial efficacy against both extracellular promastigote (IC<sub>50</sub> 9.54 and 5.42 μM, respectively) and intracellular amastigote (IC<sub>50</sub> 9.81 and 3.75 μM, respectively) forms of Leishmania donovani with negligible cytotoxicity toward the host (J774 macrophages, Vero cells). However, compound 15i effectively inhibited the parasite burden in the liver and spleen (>80%) of infected BALB/c mice. Mechanistic studies revealed that 15i triggers oxidative stress which induces bioenergetic collapse and apoptosis of the parasite by decreasing ATP production and mitochondrial membrane potential. Structure-activity analyses and pharmacokinetic studies suggest 15i as a promising antileishmanial lead and emphasize the importance of quinoline-metronidazole series as a suitable platform for the future development of antileishmanial agents.
Antileishmanial activity against Leishmania donovani MHOM/IN/80/Dd8 promastigotes harboring luciferase reporter gene at 25 uM after 48 hrs by Steady-Glo luminescence assay relative to control
|
Leishmania donovani
|
41.3
%
|
|
Journal : J Med Chem
Title : Synthesis, Biological Evaluation, Structure-Activity Relationship, and Mechanism of Action Studies of Quinoline-Metronidazole Derivatives Against Experimental Visceral Leishmaniasis.
Year : 2019
Volume : 62
Issue : 11
First Page : 5655
Last Page : 5671
Authors : Upadhyay A, Chandrakar P, Gupta S, Parmar N, Singh SK, Rashid M, Kushwaha P, Wahajuddin M, Sashidhara KV, Kar S.
Abstract : In our efforts to identify novel chemical scaffolds for the development of antileishmanial agents, a series of quinoline-metronidazole hybrid compounds was synthesized and tested against the murine model of visceral leishmaniasis. Among all synthesized derivatives, 15b and 15i showed significant antileishmanial efficacy against both extracellular promastigote (IC<sub>50</sub> 9.54 and 5.42 μM, respectively) and intracellular amastigote (IC<sub>50</sub> 9.81 and 3.75 μM, respectively) forms of Leishmania donovani with negligible cytotoxicity toward the host (J774 macrophages, Vero cells). However, compound 15i effectively inhibited the parasite burden in the liver and spleen (>80%) of infected BALB/c mice. Mechanistic studies revealed that 15i triggers oxidative stress which induces bioenergetic collapse and apoptosis of the parasite by decreasing ATP production and mitochondrial membrane potential. Structure-activity analyses and pharmacokinetic studies suggest 15i as a promising antileishmanial lead and emphasize the importance of quinoline-metronidazole series as a suitable platform for the future development of antileishmanial agents.
Antileishmanial activity against Leishmania donovani MHOM/IN/80/Dd8 amastigotes harboring luciferase reporter gene infected in mouse J774 cells at 50 uM after 48 hrs by Steady-Glo luminescence assay relative to control
|
Leishmania donovani
|
68.1
%
|
|
Journal : J Med Chem
Title : Synthesis, Biological Evaluation, Structure-Activity Relationship, and Mechanism of Action Studies of Quinoline-Metronidazole Derivatives Against Experimental Visceral Leishmaniasis.
Year : 2019
Volume : 62
Issue : 11
First Page : 5655
Last Page : 5671
Authors : Upadhyay A, Chandrakar P, Gupta S, Parmar N, Singh SK, Rashid M, Kushwaha P, Wahajuddin M, Sashidhara KV, Kar S.
Abstract : In our efforts to identify novel chemical scaffolds for the development of antileishmanial agents, a series of quinoline-metronidazole hybrid compounds was synthesized and tested against the murine model of visceral leishmaniasis. Among all synthesized derivatives, 15b and 15i showed significant antileishmanial efficacy against both extracellular promastigote (IC<sub>50</sub> 9.54 and 5.42 μM, respectively) and intracellular amastigote (IC<sub>50</sub> 9.81 and 3.75 μM, respectively) forms of Leishmania donovani with negligible cytotoxicity toward the host (J774 macrophages, Vero cells). However, compound 15i effectively inhibited the parasite burden in the liver and spleen (>80%) of infected BALB/c mice. Mechanistic studies revealed that 15i triggers oxidative stress which induces bioenergetic collapse and apoptosis of the parasite by decreasing ATP production and mitochondrial membrane potential. Structure-activity analyses and pharmacokinetic studies suggest 15i as a promising antileishmanial lead and emphasize the importance of quinoline-metronidazole series as a suitable platform for the future development of antileishmanial agents.
Antileishmanial activity against Leishmania donovani MHOM/IN/80/Dd8 amastigotes harboring luciferase reporter gene infected in mouse J774 cells at 25 uM after 48 hrs by Steady-Glo luminescence assay relative to control
|
Leishmania donovani
|
31.2
%
|
|
Journal : J Med Chem
Title : Synthesis, Biological Evaluation, Structure-Activity Relationship, and Mechanism of Action Studies of Quinoline-Metronidazole Derivatives Against Experimental Visceral Leishmaniasis.
Year : 2019
Volume : 62
Issue : 11
First Page : 5655
Last Page : 5671
Authors : Upadhyay A, Chandrakar P, Gupta S, Parmar N, Singh SK, Rashid M, Kushwaha P, Wahajuddin M, Sashidhara KV, Kar S.
Abstract : In our efforts to identify novel chemical scaffolds for the development of antileishmanial agents, a series of quinoline-metronidazole hybrid compounds was synthesized and tested against the murine model of visceral leishmaniasis. Among all synthesized derivatives, 15b and 15i showed significant antileishmanial efficacy against both extracellular promastigote (IC<sub>50</sub> 9.54 and 5.42 μM, respectively) and intracellular amastigote (IC<sub>50</sub> 9.81 and 3.75 μM, respectively) forms of Leishmania donovani with negligible cytotoxicity toward the host (J774 macrophages, Vero cells). However, compound 15i effectively inhibited the parasite burden in the liver and spleen (>80%) of infected BALB/c mice. Mechanistic studies revealed that 15i triggers oxidative stress which induces bioenergetic collapse and apoptosis of the parasite by decreasing ATP production and mitochondrial membrane potential. Structure-activity analyses and pharmacokinetic studies suggest 15i as a promising antileishmanial lead and emphasize the importance of quinoline-metronidazole series as a suitable platform for the future development of antileishmanial agents.
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
18.14
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.2
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.2
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
Antigiardial activity against Giardia duodenalis GS/M-83-H7 (ATCC 50581) incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis WB (ATCC 30957) incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis G1 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ah1 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ah2 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ac1 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ac2 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ec1 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia duodenalis Ec2 incubated for 3 days by fluorescence method
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Antigiardial activity against Giardia lamblia WB (ATCC 30957) incubated for 3 days by [3H]thymidine incorporation based assay
|
Giardia intestinalis
|
500.0
nM
|
|
Journal : J Med Chem
Title : Anti-Giardia Drug Discovery: Current Status and Gut Feelings.
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13330
Last Page : 13354
Authors : Riches A,Hart CJS,Trenholme KR,Skinner-Adams TS
Abstract : Giardia parasites are ubiquitous protozoans of global importance that impact a wide range of animals including humans. They are the most common enteric pathogen of cats and dogs in developed countries and infect ∼1 billion people worldwide. While Giardia infections can be asymptomatic, they often result in severe and chronic diseases. There is also mounting evidence that they are linked to postinfection disorders. Despite growing evidence of the widespread morbidity associated with Giardia infections, current treatment options are limited to compound classes with broad antimicrobial activity. Frontline anti-Giardia drugs are also associated with increasing drug resistance and treatment failures. To improve the health and well-being of millions, new selective anti-Giardia drugs are needed alongside improved health education initiatives. Here we discuss current treatment options together with recent advances and gaps in drug discovery. We also propose criteria to guide the discovery of new anti-Giardia compounds.
Anti-trichomonas activity against Trichomonas vaginalis JT incubated for 48 hrs by hemocytometer based eosin exclusion assay
|
Trichomonas vaginalis
|
68.0
nM
|
|
Anti-trichomonas activity against Trichomonas vaginalis CDC 085 incubated for 48 hrs by hemocytometer based eosin exclusion assay
|
Trichomonas vaginalis
|
490.0
nM
|
|
Anti-trichomonas activity against Trichomonas vaginalis GT3 incubated for 48 hrs
|
Trichomonas vaginalis
|
930.0
nM
|
|