|
Inhibition of rat lung ACE at 38 ug/ml relative to control
|
Rattus norvegicus
|
0.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 56 ug/ml relative to control
|
Rattus norvegicus
|
0.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 75 ug/ml relative to control
|
Rattus norvegicus
|
9.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 113 ug/ml relative to control
|
Rattus norvegicus
|
3.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 150 ug/ml relative to control
|
Rattus norvegicus
|
19.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 225 ug/ml relative to control
|
Rattus norvegicus
|
19.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Inhibition of rat lung ACE at 300 ug/ml relative to control
|
Rattus norvegicus
|
133.0
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensin-converting enzyme activity.
Year : 1987
Volume : 50
Issue : 4
First Page : 680
Last Page : 683
Authors : Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Hatano T, Agata I, Arichi S.
Abstract : The leaves of the persimmon Diospyros kaki, have been traditionally used for treatment of hypertensive diseases in Japan. We have studied the inhibitory effects of four flavonoids isolated from the leaves of the persimmon on angiotensin-converting enzyme activity. The four flavonoids astragalin [1], kaempferol-3-O-(2"-O-galloyl)-glucoside [2], isoquercitrin [3], and quercetin-3-O-(2"-O-galloyl)-glucoside [4] inhibited the angiotensin-converting enzyme activity in a dose-dependent fashion. Compounds 1-4 produced 67%, 53%, 33%, and 48% inhibition at a concentration of 300 micrograms/ml, respectively. The 50% inhibitory concentrations (IC50) of 1 and 2 for the angiotensin-converting enzyme were 180 micrograms/ml and 280 micrograms/ml, respectively. On the other hand, 2 and 4 were shown to have tannin activities, but 1 and 3 had no tannin activities. These results suggest that there is no relationship between the inhibition for angiotensin converting enzyme activity and the tannin activity for the four flavonoids.
|
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS trophozoites after 48 hrs by MTT/PMS assay
|
Entamoeba histolytica HM-1:IMSS
|
14.7
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
|
87.3
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.
|
Antioxidant activity assessed as DPPH free radical scavenging activity relative to control
|
None
|
16.6
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Vanillic acid glycoside and quinic acid derivatives from Gardeniae Fructus.
Year : 2006
Volume : 69
Issue : 4
First Page : 600
Last Page : 603
Authors : Kim HJ, Kim EJ, Seo SH, Shin CG, Jin C, Lee YS.
Abstract : Bioassay-directed chromatographic fractionation of an ethyl acetate extract of Gardenia jasminoides (Gardeniae Fructus) afforded a new vanillic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and five new quinic acid derivatives, methyl 5-O-caffeoyl-3-O-sinapoylquinate (2), ethyl 5-O-caffeoyl-3-O-sinapoylquinate (3), methyl 5-O-caffeoyl-4-O-sinapoylquinate (4), ethyl 5-O-caffeoyl-4-O-sinapoylquinate (5), and methyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3-methyl)glutaroylquinate (6), together with three known quinic acid derivatives, two flavonoids, two iridoids, and two phenolic compounds. The structures of new compounds were elucidated by the aid of spectroscopic methods. These compounds were assessed for antioxidant activity using three different cell-free bioassay systems and for HIV-1 integrase inhibitory activity. Five new quinic acid derivatives showed potent DPPH radical scavenging, superoxide anion scavenging, and lipid peroxidation inhibition activities. These new quinic acid derivatives also exhibited HIV-1 integrase inhibitory activity.
|
Antioxidant activity assessed as superoxide anion scavenging activity by xanthine oxidase oxidation system relative to control
|
None
|
3.4
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Vanillic acid glycoside and quinic acid derivatives from Gardeniae Fructus.
Year : 2006
Volume : 69
Issue : 4
First Page : 600
Last Page : 603
Authors : Kim HJ, Kim EJ, Seo SH, Shin CG, Jin C, Lee YS.
Abstract : Bioassay-directed chromatographic fractionation of an ethyl acetate extract of Gardenia jasminoides (Gardeniae Fructus) afforded a new vanillic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and five new quinic acid derivatives, methyl 5-O-caffeoyl-3-O-sinapoylquinate (2), ethyl 5-O-caffeoyl-3-O-sinapoylquinate (3), methyl 5-O-caffeoyl-4-O-sinapoylquinate (4), ethyl 5-O-caffeoyl-4-O-sinapoylquinate (5), and methyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3-methyl)glutaroylquinate (6), together with three known quinic acid derivatives, two flavonoids, two iridoids, and two phenolic compounds. The structures of new compounds were elucidated by the aid of spectroscopic methods. These compounds were assessed for antioxidant activity using three different cell-free bioassay systems and for HIV-1 integrase inhibitory activity. Five new quinic acid derivatives showed potent DPPH radical scavenging, superoxide anion scavenging, and lipid peroxidation inhibition activities. These new quinic acid derivatives also exhibited HIV-1 integrase inhibitory activity.
|
Antioxidant activity assessed as inhibition of 2,2'-azobis(2-amidinopropane)dihydrochloride-induced lipid peroxidation at 3.125 ug/ml by ferric thiocyanate system relative to control
|
None
|
49.9
%
|
|
Journal : J. Nat. Prod.
Title : Vanillic acid glycoside and quinic acid derivatives from Gardeniae Fructus.
Year : 2006
Volume : 69
Issue : 4
First Page : 600
Last Page : 603
Authors : Kim HJ, Kim EJ, Seo SH, Shin CG, Jin C, Lee YS.
Abstract : Bioassay-directed chromatographic fractionation of an ethyl acetate extract of Gardenia jasminoides (Gardeniae Fructus) afforded a new vanillic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside (1) and five new quinic acid derivatives, methyl 5-O-caffeoyl-3-O-sinapoylquinate (2), ethyl 5-O-caffeoyl-3-O-sinapoylquinate (3), methyl 5-O-caffeoyl-4-O-sinapoylquinate (4), ethyl 5-O-caffeoyl-4-O-sinapoylquinate (5), and methyl 3,5-di-O-caffeoyl-4-O-(3-hydroxy-3-methyl)glutaroylquinate (6), together with three known quinic acid derivatives, two flavonoids, two iridoids, and two phenolic compounds. The structures of new compounds were elucidated by the aid of spectroscopic methods. These compounds were assessed for antioxidant activity using three different cell-free bioassay systems and for HIV-1 integrase inhibitory activity. Five new quinic acid derivatives showed potent DPPH radical scavenging, superoxide anion scavenging, and lipid peroxidation inhibition activities. These new quinic acid derivatives also exhibited HIV-1 integrase inhibitory activity.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells relative to TPA
|
Human herpesvirus 4
|
570.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers.
Year : 2006
Volume : 69
Issue : 12
First Page : 1692
Last Page : 1696
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, Kimura Y.
Abstract : Ten oleanane-type triterpene glycosides, 1-10, including four new compounds, calendulaglycoside A 6'-O-methyl ester (2), calendulaglycoside A 6'-O-n-butyl ester (3), calendulaglycoside B 6'-O-n-butyl ester (5), and calendulaglycoside C 6'-O-n-butyl ester (8), along with five known flavonol glycosides, 11-15, were isolated from the flowers of marigold (Calendula officinalis). Upon evaluation of compounds 1-9 for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds, except for 1, exhibited marked anti-inflammatory activity, with ID50 values of 0.05-0.20 mg per ear. In addition, when 1-15 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, compounds 1-10 exhibited moderate inhibitory effects (IC50 values of 471-487 mol ratio/32 pmol TPA). Furthermore, upon evaluation of the cytotoxic activity against human cancer cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon cancer, leukemia, and melanoma cells.
|
Antiviral activity against RSV Long in MDCK cells assessed as inhibition of virus-induced cytopathic effect
|
Respiratory syncytial virus
|
5.9
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiviral flavonoids from the seeds of Aesculus chinensis.
Year : 2004
Volume : 67
Issue : 4
First Page : 650
Last Page : 653
Authors : Wei F, Ma SC, Ma LY, But PP, Lin RC, Khan IA.
Abstract : A bioassay-guided fractionation of an ethanol extract of the seeds of Aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). The structures of the new compounds were elucidated by spectroscopic methods including 2D NMR. All compounds were tested for antiviral activity against respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV 3), and influenza virus type A (Flu A). Compounds 1, 2, and 6 showed significant antiviral activities against RSV with IC(50) values of 4.5, 6.7, and 4.1 microg/mL and selective index (SI) values of 15.8, 32, and 63.8, respectively. Compound 8 demonstrated significant antiviral activity against Flu A with an IC(50) of 24.5 microg/mL and a SI of 16.0, respectively.
|
Cytotoxicity against MDCK cells
|
Canis lupus familiaris
|
23.4
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiviral flavonoids from the seeds of Aesculus chinensis.
Year : 2004
Volume : 67
Issue : 4
First Page : 650
Last Page : 653
Authors : Wei F, Ma SC, Ma LY, But PP, Lin RC, Khan IA.
Abstract : A bioassay-guided fractionation of an ethanol extract of the seeds of Aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). The structures of the new compounds were elucidated by spectroscopic methods including 2D NMR. All compounds were tested for antiviral activity against respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV 3), and influenza virus type A (Flu A). Compounds 1, 2, and 6 showed significant antiviral activities against RSV with IC(50) values of 4.5, 6.7, and 4.1 microg/mL and selective index (SI) values of 15.8, 32, and 63.8, respectively. Compound 8 demonstrated significant antiviral activity against Flu A with an IC(50) of 24.5 microg/mL and a SI of 16.0, respectively.
|
Antiviral activity against PIV3 in MDCK cells assessed as inhibition of virus-induced cytopathic effect
|
Human parainfluenza virus 3
|
23.4
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiviral flavonoids from the seeds of Aesculus chinensis.
Year : 2004
Volume : 67
Issue : 4
First Page : 650
Last Page : 653
Authors : Wei F, Ma SC, Ma LY, But PP, Lin RC, Khan IA.
Abstract : A bioassay-guided fractionation of an ethanol extract of the seeds of Aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). The structures of the new compounds were elucidated by spectroscopic methods including 2D NMR. All compounds were tested for antiviral activity against respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV 3), and influenza virus type A (Flu A). Compounds 1, 2, and 6 showed significant antiviral activities against RSV with IC(50) values of 4.5, 6.7, and 4.1 microg/mL and selective index (SI) values of 15.8, 32, and 63.8, respectively. Compound 8 demonstrated significant antiviral activity against Flu A with an IC(50) of 24.5 microg/mL and a SI of 16.0, respectively.
|
Antiviral activity against influenza virus type A H1N1 in MDCK cells assessed as inhibition of virus-induced cytopathic effect
|
Influenza A virus
|
500.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiviral flavonoids from the seeds of Aesculus chinensis.
Year : 2004
Volume : 67
Issue : 4
First Page : 650
Last Page : 653
Authors : Wei F, Ma SC, Ma LY, But PP, Lin RC, Khan IA.
Abstract : A bioassay-guided fractionation of an ethanol extract of the seeds of Aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). The structures of the new compounds were elucidated by spectroscopic methods including 2D NMR. All compounds were tested for antiviral activity against respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV 3), and influenza virus type A (Flu A). Compounds 1, 2, and 6 showed significant antiviral activities against RSV with IC(50) values of 4.5, 6.7, and 4.1 microg/mL and selective index (SI) values of 15.8, 32, and 63.8, respectively. Compound 8 demonstrated significant antiviral activity against Flu A with an IC(50) of 24.5 microg/mL and a SI of 16.0, respectively.
|
Inhibition of COX2 at 2.5 ug/mL
|
None
|
25.0
%
|
|
Journal : J. Nat. Prod.
Title : Expanding the ChemGPS chemical space with natural products.
Year : 2005
Volume : 68
Issue : 7
First Page : 985
Last Page : 991
Authors : Larsson J, Gottfries J, Bohlin L, Backlund A.
Abstract : Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 10 mins
|
None
|
20.4
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Saponins and polyphenols from Fadogia ancylantha (makoni tea).
Year : 2010
Volume : 73
Issue : 2
First Page : 247
Last Page : 251
Authors : Mencherini T, Picerno P, Del Gaudio P, Festa M, Capasso A, Aquino R.
Abstract : Three new saponins (1-3) and a known saponin, together with four known polyphenolic compounds, have been isolated from the fermented and dried leaves of Fadogia ancylantha (Makoni tea). The structures of compounds 1-3 were established by analysis of their spectroscopic data. Both an ethanol-water extract of F. ancylantha and its phenolic constituents showed significant free-radical-scavenging and antimicrobial activities. No cytotoxicity, as evaluated by analysis of hypodiploid nuclei in HUVEC cells using propidium iodide staining, was observed for either the plant crude extract or its constituents.
|
Cytotoxicity against human Jurkat T cells after 36 hrs by MTT assay
|
Homo sapiens
|
100.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Monoterpenoids from the aerial parts of Aruncus dioicus var. kamtschaticus and their antioxidant and cytotoxic activities.
Year : 2011
Volume : 21
Issue : 11
First Page : 3252
Last Page : 3256
Authors : Jeong SY, Jun do Y, Kim YH, Min BS, Min BK, Woo MH.
Abstract : The aerial parts of Aruncus dioicus var. kamtschaticus afforded five new monoterpenoids (1-5): 4-(erythro-6,7-dihydroxy-9-methylpent-8-enyl)furan-2(5H)-one (1, aruncin A), 2-(8-ethoxy-8-methylpropylidene)-5-hydroxy-3,6-dihydro-2H-pyran-4-carboxylic acid (2, aruncin B), 4-(hydroxymethyl)-6-(8-methylprop-7-enyl)-5,6-dihydro-2H-pyran-2-one-11-O-β-D-glucopyranoside (3, aruncide A), (3S,4S,5R,10R)-3-(10-ethoxy-11-hydroxyethyl)-4-(5-hydroxy-7-methylbut-6-enyl)oxetan-2-one-11-O-β-D-glucopyranoside (4, aruncide B), and (3S,4S,5R,7R)-5-(9-methylprop-8-enyl)-1,6-dioxabicyclo[3,2,0]heptan-2-one-7-(hydroxymethyl)-12-O-β-D-glucopyranoside (5, aruncide C). Compound 2 showed potent cytotoxicity against Jurkat T cells with an IC(50) value of 17.15 μg/mL. In addition, compounds 7 and 10 exhibited moderate antioxidant activity with IC(50) values of 46.3 and 11.7 μM, respectively.
|
Inhibition of Hepatitic C virus NS3/4A protease by FRET assay
|
Hepatitis C virus
|
10.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitory effects of polyphenols toward HCV from the mangrove plant Excoecaria agallocha L.
Year : 2012
Volume : 22
Issue : 2
First Page : 1099
Last Page : 1102
Authors : Li Y, Yu S, Liu D, Proksch P, Lin W.
Abstract : Four new polyphenols namely excoecariphenols A-D (1-4) were isolated from the Chinese mangrove plant Excoecaria agallocha L. together with 23 known phenolic compounds. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses including IR, MS, NMR, and CD data. Excoecariphenols A and B presented as the unusual flavane-based 1-thioglycosides. Part of the isolated polyphenols were tested against hepatitis C NS3-4A protease and HCV RNA in huh 7.5 cells. Excoecariphenol D, corilagin, geraniin, and chebulagic acid showed potential inhibition toward HCV NS3-4A protease with IC(50) values in a range of 3.45-9.03μM, while excoecariphenol D and corilagin inhibited HCV RNA in huh 7.5 cells significantly. A primary structure-activity relationship (SAR) is discussed.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
0.12
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of horse BChE at 2 mg/ml by Ellman's method
|
Equus caballus
|
2.54
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Antioxidant activity assessed as inhibition of DPPH radical production after 30 min by microplate assay
|
None
|
24.02
ug.mL-1
|
|
Journal : Med Chem Res
Title : -Glucosidase inhibitory and antioxidant properties and antidiabetic activity of Hypericum ascyron L.
Year : 2011
Volume : 20
Issue : 7
First Page : 809
Last Page : 816
Authors : Kang W, Song Y, Zhang L
|
Antioxidant activity assessed as inhibition of DPPH radical production at 54.05 ug/ml after 30 min by microplate assay
|
None
|
86.09
%
|
|
Journal : Med Chem Res
Title : -Glucosidase inhibitory and antioxidant properties and antidiabetic activity of Hypericum ascyron L.
Year : 2011
Volume : 20
Issue : 7
First Page : 809
Last Page : 816
Authors : Kang W, Song Y, Zhang L
|
Inhibition ofRattus norvegicus alpha-glucosidase isolated from intestine using PNPG as substrate at 0.02 uM incubated for 15 min prior to substrate addition measured after 15 min by spectrophotometric analysis
|
Rattus norvegicus
|
50.0
%
|
|
Journal : Med Chem Res
Title : -Glucosidase inhibitory and antioxidant properties and antidiabetic activity of Hypericum ascyron L.
Year : 2011
Volume : 20
Issue : 7
First Page : 809
Last Page : 816
Authors : Kang W, Song Y, Zhang L
|
Inhibition of alpha-glucosidase (unknown origin) using PNPG as substrate at 0.02 uM incubated for 15 min prior to substrate addition measured after 15 min by spectrophotometric analysis
|
Homo sapiens
|
14.38
%
|
|
Journal : Med Chem Res
Title : -Glucosidase inhibitory and antioxidant properties and antidiabetic activity of Hypericum ascyron L.
Year : 2011
Volume : 20
Issue : 7
First Page : 809
Last Page : 816
Authors : Kang W, Song Y, Zhang L
|
Inhibition of tyrosinase (unknown origin) using L-DOPA substrate at 1000 uM
|
Homo sapiens
|
54.55
%
|
|
Journal : Bioorg. Med. Chem.
Title : Biocatalytic synthesis, structural elucidation, antioxidant capacity and tyrosinase inhibition activity of long chain fatty acid acylated derivatives of phloridzin and isoquercitrin.
Year : 2013
Volume : 21
Issue : 3
First Page : 684
Last Page : 692
Authors : Ziaullah, Bhullar KS, Warnakulasuriya SN, Rupasinghe HP.
Abstract : Our present investigation describes the regioselective enzymatic acylation of two series of acylated derivatives of phloridzin and isoquercitrin with six different long chain saturated, mono- and poly-unsaturated fatty acids. The biocatalytic synthesis was optimized to achieve 81-98% yields, using immobilized lipase B, from Candida antarctica (Novozym 435), in acetone at 45°C. The synthesized esters have been analyzed by (1)H NMR, (13)C NMR spectroscopy and evaluated for their antioxidant capacity and tyrosinase inhibition, using in vitro assays. Among all the phloridzin and isoquercitrin derivatives, the greatest potential for inhibition of tyrosinase activity (p ≤ 0.05) was exhibited by the α-linolenic acid ester of isoquercitrin.
|
Inhibition of tyrosinase (unknown origin) using L-DOPA substrate at 100 uM
|
Homo sapiens
|
40.59
%
|
|
Journal : Bioorg. Med. Chem.
Title : Biocatalytic synthesis, structural elucidation, antioxidant capacity and tyrosinase inhibition activity of long chain fatty acid acylated derivatives of phloridzin and isoquercitrin.
Year : 2013
Volume : 21
Issue : 3
First Page : 684
Last Page : 692
Authors : Ziaullah, Bhullar KS, Warnakulasuriya SN, Rupasinghe HP.
Abstract : Our present investigation describes the regioselective enzymatic acylation of two series of acylated derivatives of phloridzin and isoquercitrin with six different long chain saturated, mono- and poly-unsaturated fatty acids. The biocatalytic synthesis was optimized to achieve 81-98% yields, using immobilized lipase B, from Candida antarctica (Novozym 435), in acetone at 45°C. The synthesized esters have been analyzed by (1)H NMR, (13)C NMR spectroscopy and evaluated for their antioxidant capacity and tyrosinase inhibition, using in vitro assays. Among all the phloridzin and isoquercitrin derivatives, the greatest potential for inhibition of tyrosinase activity (p ≤ 0.05) was exhibited by the α-linolenic acid ester of isoquercitrin.
|
Inhibition of tyrosinase (unknown origin) using L-DOPA substrate at 10 uM
|
Homo sapiens
|
0.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Biocatalytic synthesis, structural elucidation, antioxidant capacity and tyrosinase inhibition activity of long chain fatty acid acylated derivatives of phloridzin and isoquercitrin.
Year : 2013
Volume : 21
Issue : 3
First Page : 684
Last Page : 692
Authors : Ziaullah, Bhullar KS, Warnakulasuriya SN, Rupasinghe HP.
Abstract : Our present investigation describes the regioselective enzymatic acylation of two series of acylated derivatives of phloridzin and isoquercitrin with six different long chain saturated, mono- and poly-unsaturated fatty acids. The biocatalytic synthesis was optimized to achieve 81-98% yields, using immobilized lipase B, from Candida antarctica (Novozym 435), in acetone at 45°C. The synthesized esters have been analyzed by (1)H NMR, (13)C NMR spectroscopy and evaluated for their antioxidant capacity and tyrosinase inhibition, using in vitro assays. Among all the phloridzin and isoquercitrin derivatives, the greatest potential for inhibition of tyrosinase activity (p ≤ 0.05) was exhibited by the α-linolenic acid ester of isoquercitrin.
|
Inhibition of PTP1B (unknown origin) using p-nitrophenyl phosphate as substrate at 100 uM
|
Homo sapiens
|
50.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors.
Year : 2013
Volume : 23
Issue : 21
First Page : 5836
Last Page : 5839
Authors : Li W, Li S, Higai K, Sasaki T, Asada Y, Ohshima S, Koike K.
Abstract : Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compound library of licorice flavonoids allowed for the discovery of several compounds, including licoagrone (3), licoagrodin (4), licoagroaurone (5), and isobavachalcone (6), as new PTP1B inhibitors. It was revealed that these compounds inhibit the activity of PTP1B in different modes and with different selectivities and that they exhibit different cellular activity in the insulin-signaling pathway. Glycybenzofuran (1), a competitive PTP1B inhibitor, showed both excellent inhibitory selectivity against PTP1B and cellular activity on the insulin-stimulated Akt phosphorylation level. The similarity of its action profiling in the insulin-signaling pathway suggested its potential as a new anti-insulin-resistant drug candidate.
|
Inhibition of TRAP activity in RANKL-induced Balb/c mouse RAW264.7 cells at 10 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
82.9
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in Balb/c mouse RAW264.7 cells at 10 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
168.48
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in RANKL-induced Balb/c mouse RAW264.7 cells at 1 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
76.57
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in Balb/c mouse RAW264.7 cells at 1 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
155.6
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of sEH (unknown origin) assessed as substrate PHOME hydrolysis at 25 uM after 1 hr by fluorescence method
|
Homo sapiens
|
40.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anti-inflammatory components of Euphorbia humifusa Willd.
Year : 2014
Volume : 24
Issue : 8
First Page : 1895
Last Page : 1900
Authors : Luyen BT, Tai BH, Thao NP, Eun KJ, Cha JY, Xin MJ, Lee YM, Kim YH.
Abstract : Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC50 values as low as 18.05±1.17, 18.64±1.83, and 17.23±0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3-6, 8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-α, with IC50 values ranging from 11.1±0.9 to 45.3±1.6 μM and 14.4±0.5 to 44.5±1.2 μM, respectively.
|
Inhibition of porcine pancreatic lipase using p-nitrophenylbutyrate as substrate assessed as formation of p-nitrophenol at 100 uM preincubated for 15 mins followed by substrate addition measured after 15 mins relative to control
|
Sus scrofa
|
12.6
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pancreatic lipase inhibitory constituents from Morus alba leaves and optimization for extraction conditions.
Year : 2015
Volume : 25
Issue : 11
First Page : 2269
Last Page : 2274
Authors : Jeong JY, Jo YH, Kim SB, Liu Q, Lee JW, Mo EJ, Lee KY, Hwang BY, Lee MK.
Abstract : The leaves of Morus alba (Moraceae) have been traditionally used for the treatment of metabolic diseases including diabetes and hyperlipidemia. Thus, inhibitory effect of M. alba leaves on pancreatic lipase and their active constituents were investigated in this study. Twenty phenolic compounds including ten flavonoids, eight benzofurans, one stilbene and one chalcones were isolated from the leaves of M. alba. Among the isolated compounds, morachalcone A (20) exerted strong pancreatic lipase inhibition with IC50 value of 6.2 μM. Other phenolic compounds containing a prenyl group showed moderate pancreatic lipase inhibition with IC50 value of <50 μM. Next, extraction conditions with maximum pancreatic lipase inhibition and phenolic content were optimized using response surface methodology with three-level-three-factor Box-Behnken design. Our results suggested the optimized extraction condition for maximum pancreatic lipase inhibition and phenolic content as ethanol concentration of 74.9%; temperature 57.4 °C and sample/solvent ratio, 1/10. The pancreatic lipase inhibition and total phenolic content under optimized condition were found to be 58.5% and 26.2 μg GAE (gallic acid equivalent)/mg extract, respectively, which were well matched with the predicted value.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 1 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
16.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 3 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
33.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 10 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
20.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 30 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
23.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 100 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
20.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of mushroom tyrosinase using L-DOPA as substrate assessed as dopaquinone production at 10 uM after 5 mins by microplate reader analysis relative to control
|
Agaricus bisporus
|
4.4
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of mushroom tyrosinase using L-DOPA as substrate assessed as dopaquinone production at 100 uM after 5 mins by microplate reader analysis relative to control
|
Agaricus bisporus
|
5.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of plasmin (unknown origin) at 100 uM after 18 hrs by arianor mahogany dye-based fibrin plate assay relative to control
|
Homo sapiens
|
-2.5
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Anti-platelet activity in rat platelet rich plasma assessed as inhibition of ADP and calcium-induced platelet aggregation at 100 uM pre-incubated at 37 degC for 10 mins and measured 30 mins after ADP and calcium addition
|
Rattus norvegicus
|
36.24
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).
Year : 2015
Volume : 25
Issue : 16
First Page : 3217
Last Page : 3220
Authors : Tang Y, Ling J, Zhang P, Zhang X, Zhang N, Wang W, Li J, Li N.
Abstract : Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly.
|
Inhibition of alpha-amylase (unknown origin) relative to control
|
Homo sapiens
|
12.2
%
|
|
Journal : Bioorg. Med. Chem.
Title : From carbohydrates to drug-like fragments: Rational development of novel α-amylase inhibitors.
Year : 2015
Volume : 23
Issue : 20
First Page : 6725
Last Page : 6732
Authors : Al-Asri J, Fazekas E, Lehoczki G, Perdih A, Görick C, Melzig MF, Gyémánt G, Wolber G, Mortier J.
Abstract : Starch catabolism leading to high glucose level in blood is highly problematic in chronic metabolic diseases, such as type II diabetes and obesity. α-Amylase catalyzes the hydrolysis of starch, increasing blood sugar concentration. Its inhibition represents a promising therapeutic approach to control hyperglycaemia. However, only few drug-like molecule inhibitors without sugar moieties have been discovered so far, and little information on the enzymatic mechanism is available. This work aims at the discovery of novel small α-amylase binders using a systematic in silico methodology. 3D-pharmacophore-based high throughput virtual screening of small compounds libraries was performed to identify compounds with high α-amylase affinity. Twenty-seven compounds were selected and biologically tested, revealing IC50 values in the micromolar range and ligand efficiency higher than the one of the bound form of acarbose, which is used as a reference for α-amylase inhibition.
|
Inhibition of human recombinant carbonic anhydrase 4 preincubated for 15 mins at room temperature/6 hrs at 4 deg C by stopped-flow CO2 hydration assay
|
Homo sapiens
|
75.7
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 7 preincubated for 15 mins at room temperature/6 hrs at 4 deg C by stopped-flow CO2 hydration assay
|
Homo sapiens
|
3.8
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins at room temperature/6 hrs at 4 deg C by stopped-flow CO2 hydration assay
|
Homo sapiens
|
52.1
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 2
|
Homo sapiens
|
410.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 12
|
Homo sapiens
|
170.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of Trichomonas vaginalis adenosine-guanosine preferring ribohydrolase after 40 mins
|
Trichomonas vaginalis
|
300.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target.
Year : 2015
Volume : 25
Issue : 22
First Page : 5036
Last Page : 5039
Authors : Beck S, Muellers SN, Benzie AL, Parkin DW, Stockman BJ.
Abstract : Nucleoside salvage pathway enzymes used by Trichomonas vaginalis are distinct from the pathway involved in activation of existing 5-nitroimidazole drugs. They thus represent excellent targets for developing novel, mechanism-based antitrichomonal agents. The purine-specific adenosine/guanosine preferring ribohydrolase (AGNH) was screened against the NIH Clinical Collection to assess its druggability. Eight compounds, including five flavonoids, were identified with IC50 values ⩽10 μM and confirmed in counter screens run in the presence of detergent. The inhibitors are structurally distinct from inhibitors of the pyrimidine-specific uridine ribohydrolase (UNH) thus indicating that AGNH is a distinct, druggable target from UNH.
|
Inhibition of Trichomonas vaginalis adenosine-guanosine preferring ribohydrolase after 40 mins in presence of 0.01% triton X-100
|
Trichomonas vaginalis
|
900.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target.
Year : 2015
Volume : 25
Issue : 22
First Page : 5036
Last Page : 5039
Authors : Beck S, Muellers SN, Benzie AL, Parkin DW, Stockman BJ.
Abstract : Nucleoside salvage pathway enzymes used by Trichomonas vaginalis are distinct from the pathway involved in activation of existing 5-nitroimidazole drugs. They thus represent excellent targets for developing novel, mechanism-based antitrichomonal agents. The purine-specific adenosine/guanosine preferring ribohydrolase (AGNH) was screened against the NIH Clinical Collection to assess its druggability. Eight compounds, including five flavonoids, were identified with IC50 values ⩽10 μM and confirmed in counter screens run in the presence of detergent. The inhibitors are structurally distinct from inhibitors of the pyrimidine-specific uridine ribohydrolase (UNH) thus indicating that AGNH is a distinct, druggable target from UNH.
|
Antileishmanial activity against amastigote Leishmania amazonensis
|
Leishmania amazonensis
|
0.78
ug.mL-1
|
|
Journal : MedChemComm
Title : Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?
Year : 2016
Volume : 7
Issue : 2
First Page : 214
Last Page : 223
Authors : Glaser J, Holzgrabe U
|
Antichlamydial activity against Chlamydia pneumoniae K7 infected in HL cells assessed as chlamydial inhibition at 50 uM after 70 hrs by fluorescent microscopic analysis
|
Chlamydia pneumoniae
|
38.0
%
|
|
Journal : J Nat Prod
Title : Identification of Privileged Antichlamydial Natural Products by a Ligand-Based Strategy.
Year : 2017
Volume : 80
Issue : 10
First Page : 2602
Last Page : 2608
Authors : Karhu E, Isojärvi J, Vuorela P, Hanski L, Fallarero A.
Abstract : The obligate intracellular pathogen Chlamydia pneumoniae remains a difficult target for antimicrobial therapy. Owing to the permeability barrier placed by bacterial and host vacuolar membranes, as well as the propensity of the bacterium for persistent infections, treatment failures are common. Despite the urgent need for new antichlamydial compounds, their discovery is challenged by the technically demanding assay procedures and lack of validated targets. An alternative strategy of using naturally occurring compounds and their derivatives against C. pneumoniae is presented. The strategy consists of the application of ligand-based virtual screening to a natural product library of 502 compounds with the ChemGPS-NP chemography tool followed by in vitro antichlamydial assays. The reference set used for the 2D similarity search was constructed of 19 known antichlamydial compounds of plant origin. Based on the similarity screen, 53 virtual hits were selected for in vitro testing. Six compounds (leads) were identified that cause ≥50% C. pneumoniae growth inhibition and showed no impact on host cell viability. The leads fall into completely new antichlamydial chemotypes, one of them being mycophenolic acid (IC50 value 0.3 μM). The outcome indicates that using this flipped, target-independent strategy is useful for facilitating the antimicrobial lead discovery against challenging microbes.
|
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
|
18.79
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
-1.78
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
10.08
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
60.53
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
25.15
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
1.9
%
|
|
|
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
|
3.22
%
|
|
|
Inhibition of LSD1 (unknown origin) by fluorescence assay
|
Homo sapiens
|
950.0
nM
|
|
Journal : Bioorg Med Chem
Title : Flavone-based natural product agents as new lysine-specific demethylase 1 inhibitors exhibiting cytotoxicity against breast cancer cells in vitro.
Year : 2019
Volume : 27
Issue : 2
First Page : 370
Last Page : 374
Authors : Xu X, Peng W, Liu C, Li S, Lei J, Wang Z, Kong L, Han C.
Abstract : Lysine-specific demethylase 1 (LSD1) has recently emerged as a therapeutic target for cancer. However, almost all LSD1 inhibitors developed to date are chemo-synthesised molecules. In this study, the LSD1 inhibitory activity of 12 natural flavones, including four aglycones and their corresponding monoglycosides and diglucosides, was evaluated. Based on the structure-activity relationships, LSD1 inhibition activity was greater for flavonoid monoglycosides than their aglycones lacking the sugar moiety. The effects of isoquercitrin, which exhibited optimal LSD1 inhibitory activity, on cancer cell properties were evaluated. Isoquercitrin induced the expression of key proteins in the mitochondrial-mediated apoptosis pathway and caused apoptosis in LSD1-overexpressing MDA-MB-231 cells via the inhibition of LSD1. These findings suggest that natural LSD1 inhibitors, and particularly isoquercitrin, are promising for cancer treatment.
|
Inhibition of PCSK9 mRNA expression in human HuH7 cells at 2 uM after 24 hrs by qRT-PCR assay relative to control
|
Homo sapiens
|
20.0
%
|
|
Journal : Eur J Med Chem
Title : Small molecules as inhibitors of PCSK9: Current status and future challenges.
Year : 2019
Volume : 162
First Page : 212
Last Page : 233
Authors : Xu S, Luo S, Zhu Z, Xu J.
Abstract : Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulating lipoprotein metabolism by binding to low-density lipoprotein receptors (LDLRs), leading to their degradation. LDL cholesterol (LDL-C) lowering drugs that operate through the inhibition of PCSK9 are being pursued for the management of hypercholesterolemia and reducing its associated atherosclerotic cardiovascular disease (CVD) risk. Two PCSK9-blocking monoclonal antibodies (mAbs), alirocumab and evolocumab, were approved in 2015. However, the high costs of PCSK9 antibody drugs impede their prior authorization practices and reduce their long-term adherence. Given the potential of small-molecule drugs, the development of small-molecule PCSK9 inhibitors has attracted considerable attention. This article provides an overview of the recent development of small-molecule PCSK9 inhibitors disclosed in the literature and patent applications, and different approaches that have been pursued to modulate the functional activity of PCSK9 using small molecules are described. Challenges and potential strategies in developing small-molecule PCSK9 inhibitors are also discussed.
|
Inhibition of ATP synthase in Escherichia coli relative to control
|
Escherichia coli
|
40.0
%
|
|
Journal : Eur J Med Chem
Title : Recent advancements in mechanistic studies and structure activity relationship of FoF1 ATP synthase inhibitor as antimicrobial agent.
Year : 2019
Volume : 182
First Page : 111644
Last Page : 111644
Authors : Narang R, Kumar R, Kalra S, Nayak SK, Khatik GL, Kumar GN, Sudhakar K, Singh SK.
Abstract : The emergence of drug resistance in infectious microbial strains can be overcome by development of novel drug molecules against unexploited microbial target. The success of Bedaquiline in recent years, as FoF1 ATP synthase inhibitor against XDR and MDR mycobacterium strains, has resulted in further exploration to identify more potent and safe drug molecules against resistant strains. FoF1 ATP synthase is the main energy production enzyme in almost all eukaryotes and prokaryotes. Development of bacterial ATP synthase inhibitors is a safe approach, without causing harm to mammalian cells due to structural difference between bacterial and mammalian ATP synthase target sites. This review emphasizes on providing the structural insights for FoF1 ATP synthase of different prokaryotes and will help in the design of new potent antimicrobial agents with better efficacy. Further, applications of synthetic and natural active antimicrobial ATP synthase inhibitors, reported by different research groups are summarized. Their SAR and mode of actions are also analysed.
|
Hypolipidemic activity against oleic acid/palmitic acid-induced hyperlipidemia in human HepG2 cells assessed as reduction in triglycerides content relative to control group
|
Homo sapiens
|
30.42
%
|
|
