|
Inhibition of cell free transcription/translation by Escherichia coli s30 bacterial extract.
|
Escherichia coli
|
40.0
nM
|
|
Journal : J. Med. Chem.
Title : New inhibitors of bacterial protein synthesis from a combinatorial library of macrocycles.
Year : 2002
Volume : 45
Issue : 16
First Page : 3430
Last Page : 3439
Authors : Jefferson EA, Arakawa S, Blyn LB, Miyaji A, Osgood SA, Ranken R, Risen LM, Swayze EE.
Abstract : A mixture-based combinatorial library of 14-membered macrocycles was synthesized to target ribosomal RNA and uncover a new class of antibacterial agents. High-throughput screening identified a macrocyclic mixture that inhibited cell-free-coupled transcription/translation in Escherichia coli-derived extracts, with an IC(50) value in the 25-50 microM range. In a follow-up library of 64 single macrocycles, 8 gave IC(50) values ranging from 12 to 50 microM in the cell-free protein synthesis inhibition assay. Some of the macrocycles were screened in a translation inhibition assay, and IC(50) values generally paralleled those obtained in the uncoupled transcription/translation assay. Additional analogues were prepared in a preliminary structure-activity relationship study, and more potent macrocycles were identified with low micromolar activity (IC(50) values = 2-3 microM). Some of these macrocycles displayed antibacterial activity against lipopolysaccharide mutant E. coli bacterial cells (IC(50) values = 12-50 microM).
|
In vitro inhibition of translation in luciferase SP6 control plasmid
|
None
|
80.0
nM
|
|
Journal : J. Med. Chem.
Title : New inhibitors of bacterial protein synthesis from a combinatorial library of macrocycles.
Year : 2002
Volume : 45
Issue : 16
First Page : 3430
Last Page : 3439
Authors : Jefferson EA, Arakawa S, Blyn LB, Miyaji A, Osgood SA, Ranken R, Risen LM, Swayze EE.
Abstract : A mixture-based combinatorial library of 14-membered macrocycles was synthesized to target ribosomal RNA and uncover a new class of antibacterial agents. High-throughput screening identified a macrocyclic mixture that inhibited cell-free-coupled transcription/translation in Escherichia coli-derived extracts, with an IC(50) value in the 25-50 microM range. In a follow-up library of 64 single macrocycles, 8 gave IC(50) values ranging from 12 to 50 microM in the cell-free protein synthesis inhibition assay. Some of the macrocycles were screened in a translation inhibition assay, and IC(50) values generally paralleled those obtained in the uncoupled transcription/translation assay. Additional analogues were prepared in a preliminary structure-activity relationship study, and more potent macrocycles were identified with low micromolar activity (IC(50) values = 2-3 microM). Some of these macrocycles displayed antibacterial activity against lipopolysaccharide mutant E. coli bacterial cells (IC(50) values = 12-50 microM).
|
IC50 was measured as concentration causing 50% inhibition of lysosomal phospholipase A1 activity.
|
None
|
39.0
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Synthesis and antimicrobial and toxicological studies of amino acid and peptide derivatives of kanamycin A and netilmicin.
Year : 1995
Volume : 38
Issue : 23
First Page : 4710
Last Page : 4719
Authors : Kotretsou S, Mingeot-Leclercq MP, Constantinou-Kokotou V, Brasseur R, Georgiadis MP, Tulkens PM.
Abstract : Amino acid and peptide derivatives of aminoglycosides have been obtained by substitution of the 1-N or 6'-N amino functions of kanamycin A and netilmicin via the temporary complexation of vicinal and nonvicinal amino and hydroxy functions by copper ion [1-N kanamycin A derivatives: L-Ala (6a), D-Ala (6b), Gly (6c), L-Asp (6d), L-Ala-L-Ala (6e). 6'-N kanamycin A derivatives: L-Ala (3a), D-Ala (3b), Gly (3c), L-Ala-L-Ala (3e), L-Leu (3f). 6'-N netilmicin derivatives: L-Ala (9a), D-Ala (9b), Gly (9c), L-Asp (9d), L-Ala-L-Ala (9e)]. Characterization was made by FAB-MS, IR, 1H-NMR, and 13C-NMR. All derivatives were essentially inactive. The nephrotoxic potential of the derivatives obtained in sufficient quantities (3b,e and 9a-e) was assessed by measuring their inhibitory potential toward the activity of lysosomal phospholipase A1 acting on phosphatidylcholine embedded in negatively-charged membranes. One compound, 6'-N-L-Ala-netilmicin (9a), showed a 2-fold decrease of inhibitory potency compared to its parent drug. A conformational analysis revealed that it adopts two equally probable conformations and orientations when interacting with phosphatidylinositol. The first in which the drug lies parallel to the hydrophobic-hydrophilic interface, is similar to that of netilmicin. The second, in which the drug inserts itself in the bilayer across the hydrophilic/hydrophobic interface, is similar to that described for streptomycin, an almost non-nephrotoxic aminoglycoside.
|
Antimycobacterial activity of compound against Mycobacterium tuberculosis H37Rv at 5 ug/mL
|
Mycobacterium tuberculosis
|
90.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antituberculous activity of some aryl semicarbazone derivatives.
Year : 2004
Volume : 14
Issue : 15
First Page : 3923
Last Page : 3924
Authors : Sriram D, Yogeeswari P, Thirumurugan R.
Abstract : During the course of our work on the synthesis and screening of new drugs for tuberculosis, we have identified N1-(4-acetamido phenyl)-N4-(2-nitro benzylidene) semicarbazone (1b), which inhibited in vitro Mycobacterium tuberculosis H(37)Rv; 100% inhibition at 1.56 microg/mL. This paper is first of its kind in which aryl semicarbazones are reported to possess antimycobacterials potency greater than p-aminosalicylic acid, ethionamide, ethambutol, ciprofloxacin and kanamycin.
|
Inhibition of protein synthesis in Escherichia coli S30 extracts by coupled transcription-translation assay
|
Escherichia coli
|
400.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structure-activity relationships of novel antibacterial translation inhibitors: 3,5-diamino-piperidinyl triazines.
Year : 2006
Volume : 16
Issue : 20
First Page : 5451
Last Page : 5456
Authors : Zhou Y, Sun Z, Froelich JM, Hermann T, Wall D.
Abstract : Structure-activity relationships of the 3,5-diamino-piperidinyl triazine series, a novel class of bacterial translation inhibitors, are described. Optimization was focused on the triazine C-4 position in which aromatic substituents that contained electron-withdrawing groups led to potent inhibitors. The initial lack of antibacterial activity was correlated with poor cellular penetration. Whole cell antibacterial activity was achieved by linking additional aromatic moieties at the triazine C-4 position.
|
Inhibition of protein synthesis in Escherichia coli by coupled transcription-translation assay
|
Escherichia coli
|
400.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and SAR of 3,5-diamino-piperidine derivatives: novel antibacterial translation inhibitors as aminoglycoside mimetics.
Year : 2007
Volume : 17
Issue : 5
First Page : 1206
Last Page : 1210
Authors : Zhou Y, Gregor VE, Ayida BK, Winters GC, Sun Z, Murphy D, Haley G, Bailey D, Froelich JM, Fish S, Webber SE, Hermann T, Wall D.
Abstract : Aminoglycoside antibiotics target an internal RNA loop within the bacterial ribosomal decoding site. Here, we describe the synthesis and SAR of novel 3,5-diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as inhibitors of bacterial translation and growth.
|
Antimicrobial activity against Mycobacterium tuberculosis H37Ra by microplate alamar blue assay
|
Mycobacterium tuberculosis H37Ra
|
2.5
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Biomimetic transformation and biological activities of Globiferin, a terpenoid benzoquinone from Cordia globifera.
Year : 2009
Volume : 72
Issue : 5
First Page : 861
Last Page : 865
Authors : Dettrakul S, Surerum S, Rajviroongit S, Kittakoop P.
Abstract : A new 10-membered ring meroterpene (1), named globiferin, was isolated from root extracts of Cordia globifera. Biomimetic transformations of 1 and its derivatives, either by acid cyclization or by Cope rearrangement, provided information relating to the biogenesis of cordiachromes A-C. Globiferin (1) underwent Cope rearrangement upon refluxing in xylene and DMSO-d(6) to yield cordiachrome C (3) and cordiaquinol C (4), respectively. Heating in DMSO-d(6) resulted in an unexpected reduction of a quinone moiety. Globiferin diacetate (1b) cyclized under acidic conditions to give compounds 10 and 11, respective derivatives of natural cordiachromes B (2) and A (12). The present study indicates that globiferin (1) is a genuine intermediate for the biosynthesis of cordiachromes in Cordia species. Compounds 1 and 3 exhibited significant antimycobacterial activity, with MIC values of 6.2 and 1.5 mug/mL, respectively. Antimalarial, antifungal, and cytotoxic activities of 1 and its derivatives were also evaluated.
|
Antibacterial activity against Salmonella enterica serovars virchow isolate 101591 at pH 5.7 by bioluminescence assay
|
Salmonella enterica subsp. enterica serovar Virchow
|
130.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow.
Year : 2008
Volume : 52
Issue : 3
First Page : 920
Last Page : 926
Authors : Menashe O, Kaganskaya E, Baasov T, Yaron S.
Abstract : The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria during intracellular studies. Given the evidence that aminoglycosides can penetrate the eukaryotic cell membrane, the goal of this study was to examine the influence of aminoglycosides on macrophage-associated Salmonella. Herein, we show that gentamicin, kanamycin, and tobramycin at concentrations between 15 to 150 microg ml(-1) do not kill intracellular Salmonella but have other effects on the bacterial physiology. By using Salmonella enterica serovars Typhimurium and Virchow harboring luciferase reporter plasmid, we observed that the light produced by intracellular Salmonella declined immediately upon exposure to aminoglycosides, indicating that the bacteria were under stress. The extent of this effect was dependent on the macrophage host, on the identity of the aminoglycoside and its concentration, on the exposure time, and on the Salmonella serovar. Salmonella associated with Nramp1-negative macrophages, in which the phagosomal pH is higher, were more susceptible to aminoglycosides than Salmonella associated with Nramp1-expressing macrophages. These results verify that aminoglycosides affect intracellular bacteria and that the extent of this effect is dependent on the acidity level within the phagosome, suggesting that for the study of intracellular bacteria, the aminoglycoside concentration should be limited to two to five times the MIC for the bacterial strain studied. This precaution should guarantee the complete execution of extracellular bacteria with minimal effects on the intracellular bacteria and the host cells.
|
Antibacterial activity against Salmonella enterica serovars virchow isolate 101591 at pH 7.0 by bioluminescence assay
|
Salmonella enterica subsp. enterica serovar Virchow
|
6.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow.
Year : 2008
Volume : 52
Issue : 3
First Page : 920
Last Page : 926
Authors : Menashe O, Kaganskaya E, Baasov T, Yaron S.
Abstract : The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria during intracellular studies. Given the evidence that aminoglycosides can penetrate the eukaryotic cell membrane, the goal of this study was to examine the influence of aminoglycosides on macrophage-associated Salmonella. Herein, we show that gentamicin, kanamycin, and tobramycin at concentrations between 15 to 150 microg ml(-1) do not kill intracellular Salmonella but have other effects on the bacterial physiology. By using Salmonella enterica serovars Typhimurium and Virchow harboring luciferase reporter plasmid, we observed that the light produced by intracellular Salmonella declined immediately upon exposure to aminoglycosides, indicating that the bacteria were under stress. The extent of this effect was dependent on the macrophage host, on the identity of the aminoglycoside and its concentration, on the exposure time, and on the Salmonella serovar. Salmonella associated with Nramp1-negative macrophages, in which the phagosomal pH is higher, were more susceptible to aminoglycosides than Salmonella associated with Nramp1-expressing macrophages. These results verify that aminoglycosides affect intracellular bacteria and that the extent of this effect is dependent on the acidity level within the phagosome, suggesting that for the study of intracellular bacteria, the aminoglycoside concentration should be limited to two to five times the MIC for the bacterial strain studied. This precaution should guarantee the complete execution of extracellular bacteria with minimal effects on the intracellular bacteria and the host cells.
|
Antibacterial activity against Salmonella enterica serovars Typhimurium ATCC 14028 at pH 7.0 by bioluminescence assay
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
3.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow.
Year : 2008
Volume : 52
Issue : 3
First Page : 920
Last Page : 926
Authors : Menashe O, Kaganskaya E, Baasov T, Yaron S.
Abstract : The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria during intracellular studies. Given the evidence that aminoglycosides can penetrate the eukaryotic cell membrane, the goal of this study was to examine the influence of aminoglycosides on macrophage-associated Salmonella. Herein, we show that gentamicin, kanamycin, and tobramycin at concentrations between 15 to 150 microg ml(-1) do not kill intracellular Salmonella but have other effects on the bacterial physiology. By using Salmonella enterica serovars Typhimurium and Virchow harboring luciferase reporter plasmid, we observed that the light produced by intracellular Salmonella declined immediately upon exposure to aminoglycosides, indicating that the bacteria were under stress. The extent of this effect was dependent on the macrophage host, on the identity of the aminoglycoside and its concentration, on the exposure time, and on the Salmonella serovar. Salmonella associated with Nramp1-negative macrophages, in which the phagosomal pH is higher, were more susceptible to aminoglycosides than Salmonella associated with Nramp1-expressing macrophages. These results verify that aminoglycosides affect intracellular bacteria and that the extent of this effect is dependent on the acidity level within the phagosome, suggesting that for the study of intracellular bacteria, the aminoglycoside concentration should be limited to two to five times the MIC for the bacterial strain studied. This precaution should guarantee the complete execution of extracellular bacteria with minimal effects on the intracellular bacteria and the host cells.
|
Antibacterial activity against Salmonella enterica serovars Typhimurium ATCC 14028 at pH 5.7 by bioluminescence assay
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
29.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow.
Year : 2008
Volume : 52
Issue : 3
First Page : 920
Last Page : 926
Authors : Menashe O, Kaganskaya E, Baasov T, Yaron S.
Abstract : The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria during intracellular studies. Given the evidence that aminoglycosides can penetrate the eukaryotic cell membrane, the goal of this study was to examine the influence of aminoglycosides on macrophage-associated Salmonella. Herein, we show that gentamicin, kanamycin, and tobramycin at concentrations between 15 to 150 microg ml(-1) do not kill intracellular Salmonella but have other effects on the bacterial physiology. By using Salmonella enterica serovars Typhimurium and Virchow harboring luciferase reporter plasmid, we observed that the light produced by intracellular Salmonella declined immediately upon exposure to aminoglycosides, indicating that the bacteria were under stress. The extent of this effect was dependent on the macrophage host, on the identity of the aminoglycoside and its concentration, on the exposure time, and on the Salmonella serovar. Salmonella associated with Nramp1-negative macrophages, in which the phagosomal pH is higher, were more susceptible to aminoglycosides than Salmonella associated with Nramp1-expressing macrophages. These results verify that aminoglycosides affect intracellular bacteria and that the extent of this effect is dependent on the acidity level within the phagosome, suggesting that for the study of intracellular bacteria, the aminoglycoside concentration should be limited to two to five times the MIC for the bacterial strain studied. This precaution should guarantee the complete execution of extracellular bacteria with minimal effects on the intracellular bacteria and the host cells.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
17.57
%
|
|
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
|
-5.91
%
|
|
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.
|
Antibacterial activity against Bacillus subtilis assessed as survival after 24 hrs by MTT assay
|
Bacillus subtilis
|
8.9
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Potentiating 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives against antibacterial agents: design, synthesis and biology analysis.
Year : 2013
Volume : 65
First Page : 456
Last Page : 463
Authors : Wang ZC, Duan YT, Qin YJ, Wang PF, Luo Y, Wen Q, Yang YA, Sun J, Hu Y, Sang YL, Zhu HL.
Abstract : A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.
|
Antibacterial activity against Bacillus thuringiensis assessed as survival after 24 hrs by MTT assay
|
Bacillus thuringiensis
|
9.5
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Potentiating 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives against antibacterial agents: design, synthesis and biology analysis.
Year : 2013
Volume : 65
First Page : 456
Last Page : 463
Authors : Wang ZC, Duan YT, Qin YJ, Wang PF, Luo Y, Wen Q, Yang YA, Sun J, Hu Y, Sang YL, Zhu HL.
Abstract : A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.
|
Antibacterial activity against Pseudomonas aeruginosa assessed as survival after 24 hrs by MTT assay
|
Pseudomonas aeruginosa
|
6.8
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Potentiating 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives against antibacterial agents: design, synthesis and biology analysis.
Year : 2013
Volume : 65
First Page : 456
Last Page : 463
Authors : Wang ZC, Duan YT, Qin YJ, Wang PF, Luo Y, Wen Q, Yang YA, Sun J, Hu Y, Sang YL, Zhu HL.
Abstract : A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.
|
Antibacterial activity against Escherichia coli assessed as survival after 24 hrs by MTT assay
|
Escherichia coli
|
47.3
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Potentiating 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives against antibacterial agents: design, synthesis and biology analysis.
Year : 2013
Volume : 65
First Page : 456
Last Page : 463
Authors : Wang ZC, Duan YT, Qin YJ, Wang PF, Luo Y, Wen Q, Yang YA, Sun J, Hu Y, Sang YL, Zhu HL.
Abstract : A series of novel 1-(2-hydroxypropyl)-2-styryl-5-nitroimidazole derivatives had been designed, synthesized, isolated and evaluated as potentiators of antibacterial agents. All these synthesized compounds were determined by elemental analysis, (1)H NMR, and MS. Their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus thuringiensis and Bacillus subtilis by MTT method as potential FabH inhibitory. The results showed that compound 30 exhibited the most potent E. coli FabH inhibitory activity with IC50 of 4.6 μM. Molecular modeling simulation studies were performed in order to predict the biological activities of the proposed compounds. All compounds have been tested for toxicity by MTT assay on human macrophage.
|
Cytotoxicity against african green monkey Vero cells after 72 hrs by MTS-PMS assay
|
Chlorocebus sabaeus
|
100.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Chlorinated coumarins from the polypore mushroom Fomitopsis officinalis and their activity against Mycobacterium tuberculosis.
Year : 2013
Volume : 76
Issue : 10
First Page : 1916
Last Page : 1922
Authors : Hwang CH, Jaki BU, Klein LL, Lankin DC, McAlpine JB, Napolitano JG, Fryling NA, Franzblau SG, Cho SH, Stamets PE, Wang Y, Pauli GF.
Abstract : An EtOH extract of the polypore mushroom Fomitopsis officinalis afforded two new naturally occurring chlorinated coumarins, which were identified as the previously synthesized compounds 6-chloro-4-phenyl-2H-chromen-2-one (1) and ethyl 6-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (2). The structures of the two isolates were deduced by ab initio spectroscopic methods and confirmed by chemical synthesis. In addition, an analogue of each was synthesized as 7-chloro-4-phenyl-2H-chromen-2-one (3) and ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (4). All four compounds were characterized physicochemically, and their antimicrobial activity profiles revealed a narrow spectrum of activity with lowest MICs against the Mycobacterium tuberculosis complex.
|
Antibacterial activity against Mycobacterium smegmatis after 18 hrs by turbidity assay
|
Mycobacterium smegmatis
|
1.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Stereochemical assignment of the fungal metabolites pestalotiopsones D and E through enantiopure synthesis.
Year : 2013
Volume : 76
Issue : 11
First Page : 2054
Last Page : 2059
Authors : Beekman AM, Barrow RA.
Abstract : The pestalotiopsones are fungal metabolites isolated from an endophytic fungus Pestalotiopsis sp. found in the mangrove Rhizophora mucronata, used in traditional Chinese medicine to treat symptoms of dysentery. The absolute configurations of pestalotiopsones D (4) and E (5) were elucidated through total synthesis of both the R and S enantiomers, allowing for the assignment of the stereochemistry of the natural compounds as the (+)-S enantiomers. The key steps include homologation of a substituted benzoic acid to the appropriate phenylacetate derivative using Birch reductive alkylation, an oxa-Michael cyclization induced by microwave irradiation to form the chromanone substructure, and an IBX-mediated dehydrogenation yielding the chromone skeleton. Assessment of the synthetic compounds against clinical pathogens was performed.
|
Antibacterial activity against Escherichia coli after 18 hrs by turbidity assay
|
Escherichia coli
|
1.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Stereochemical assignment of the fungal metabolites pestalotiopsones D and E through enantiopure synthesis.
Year : 2013
Volume : 76
Issue : 11
First Page : 2054
Last Page : 2059
Authors : Beekman AM, Barrow RA.
Abstract : The pestalotiopsones are fungal metabolites isolated from an endophytic fungus Pestalotiopsis sp. found in the mangrove Rhizophora mucronata, used in traditional Chinese medicine to treat symptoms of dysentery. The absolute configurations of pestalotiopsones D (4) and E (5) were elucidated through total synthesis of both the R and S enantiomers, allowing for the assignment of the stereochemistry of the natural compounds as the (+)-S enantiomers. The key steps include homologation of a substituted benzoic acid to the appropriate phenylacetate derivative using Birch reductive alkylation, an oxa-Michael cyclization induced by microwave irradiation to form the chromanone substructure, and an IBX-mediated dehydrogenation yielding the chromone skeleton. Assessment of the synthetic compounds against clinical pathogens was performed.
|
Antibacterial activity against Pseudomonas aeruginosa after 18 hrs by turbidity assay
|
Pseudomonas aeruginosa
|
209.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Stereochemical assignment of the fungal metabolites pestalotiopsones D and E through enantiopure synthesis.
Year : 2013
Volume : 76
Issue : 11
First Page : 2054
Last Page : 2059
Authors : Beekman AM, Barrow RA.
Abstract : The pestalotiopsones are fungal metabolites isolated from an endophytic fungus Pestalotiopsis sp. found in the mangrove Rhizophora mucronata, used in traditional Chinese medicine to treat symptoms of dysentery. The absolute configurations of pestalotiopsones D (4) and E (5) were elucidated through total synthesis of both the R and S enantiomers, allowing for the assignment of the stereochemistry of the natural compounds as the (+)-S enantiomers. The key steps include homologation of a substituted benzoic acid to the appropriate phenylacetate derivative using Birch reductive alkylation, an oxa-Michael cyclization induced by microwave irradiation to form the chromanone substructure, and an IBX-mediated dehydrogenation yielding the chromone skeleton. Assessment of the synthetic compounds against clinical pathogens was performed.
|
Antibacterial activity against Staphylococcus epidermidis after 18 hrs by turbidity assay
|
Staphylococcus epidermidis
|
90.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Stereochemical assignment of the fungal metabolites pestalotiopsones D and E through enantiopure synthesis.
Year : 2013
Volume : 76
Issue : 11
First Page : 2054
Last Page : 2059
Authors : Beekman AM, Barrow RA.
Abstract : The pestalotiopsones are fungal metabolites isolated from an endophytic fungus Pestalotiopsis sp. found in the mangrove Rhizophora mucronata, used in traditional Chinese medicine to treat symptoms of dysentery. The absolute configurations of pestalotiopsones D (4) and E (5) were elucidated through total synthesis of both the R and S enantiomers, allowing for the assignment of the stereochemistry of the natural compounds as the (+)-S enantiomers. The key steps include homologation of a substituted benzoic acid to the appropriate phenylacetate derivative using Birch reductive alkylation, an oxa-Michael cyclization induced by microwave irradiation to form the chromanone substructure, and an IBX-mediated dehydrogenation yielding the chromone skeleton. Assessment of the synthetic compounds against clinical pathogens was performed.
|
Antibacterial activity against Escherichia coli after 12 hrs by MTT assay
|
Escherichia coli
|
47.3
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Design and synthesis of 2-styryl of 5-Nitroimidazole derivatives and antimicrobial activities as FabH inhibitors.
Year : 2014
Volume : 76
First Page : 387
Last Page : 396
Authors : Duan YT, Wang ZC, Sang YL, Tao XX, Teraiya SB, Wang PF, Wen Q, Zhou XJ, Ding L, Yang YH, Zhu HL.
Abstract : A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by (1)H NMR, MS, and elemental analysis. E. coli β-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC₅₀ of 9.0-36.4 μg/mL and compound 47 with IC₅₀ of 6.3-34.3 μg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.
|
Antibacterial activity against Pseudomonas aeruginosa after 12 hrs by MTT assay
|
Pseudomonas aeruginosa
|
6.8
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Design and synthesis of 2-styryl of 5-Nitroimidazole derivatives and antimicrobial activities as FabH inhibitors.
Year : 2014
Volume : 76
First Page : 387
Last Page : 396
Authors : Duan YT, Wang ZC, Sang YL, Tao XX, Teraiya SB, Wang PF, Wen Q, Zhou XJ, Ding L, Yang YH, Zhu HL.
Abstract : A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by (1)H NMR, MS, and elemental analysis. E. coli β-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC₅₀ of 9.0-36.4 μg/mL and compound 47 with IC₅₀ of 6.3-34.3 μg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.
|
Antibacterial activity against Bacillus subtilis after 12 hrs by MTT assay
|
Bacillus subtilis
|
8.9
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Design and synthesis of 2-styryl of 5-Nitroimidazole derivatives and antimicrobial activities as FabH inhibitors.
Year : 2014
Volume : 76
First Page : 387
Last Page : 396
Authors : Duan YT, Wang ZC, Sang YL, Tao XX, Teraiya SB, Wang PF, Wen Q, Zhou XJ, Ding L, Yang YH, Zhu HL.
Abstract : A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by (1)H NMR, MS, and elemental analysis. E. coli β-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC₅₀ of 9.0-36.4 μg/mL and compound 47 with IC₅₀ of 6.3-34.3 μg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.
|
Antibacterial activity against Bacillus thuringiensis after 12 hrs by MTT assay
|
Bacillus thuringiensis
|
9.5
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Design and synthesis of 2-styryl of 5-Nitroimidazole derivatives and antimicrobial activities as FabH inhibitors.
Year : 2014
Volume : 76
First Page : 387
Last Page : 396
Authors : Duan YT, Wang ZC, Sang YL, Tao XX, Teraiya SB, Wang PF, Wen Q, Zhou XJ, Ding L, Yang YH, Zhu HL.
Abstract : A series of 2-Styryl-5-Nitroimidazole derivatives (25-48) have been synthesized and their biological activities were also evaluated against two Gram-negative bacterial strains: Escherichia coli and Pseudomonas aeruginosa and two Gram-positive bacterial strains: Bacillus subtilis and Bacillus thuringiensis as potential FabH inhibitors. All the compounds were structurally determined by (1)H NMR, MS, and elemental analysis. E. coli β-ketoacyl-acyl carrier protein synthase III inhibitory assay and docking simulation indicated that compound 33 with IC₅₀ of 9.0-36.4 μg/mL and compound 47 with IC₅₀ of 6.3-34.3 μg/mL against bacterial strains were most potent inhibitors of E. coli FabH. And more, compounds 33 and 47 which possessed a broad-spectrum of antibacterial activities didn't exhibit any toxicity towards macrophage.
|
Antibacterial activity against Escherichia coli after 24 hrs by MTT method
|
Escherichia coli
|
46.3
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.
Year : 2014
Volume : 24
Issue : 22
First Page : 2579
Last Page : 2583
Authors : Qin YJ, Wang PF, Makawana JA, Wang ZC, Wang ZN, Yan-Gu, Jiang AQ, Zhu HL.
Abstract : A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.
|
Antibacterial activity against Pseudomonas aeruginosa after 24 hrs by MTT method
|
Pseudomonas aeruginosa
|
6.8
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.
Year : 2014
Volume : 24
Issue : 22
First Page : 2579
Last Page : 2583
Authors : Qin YJ, Wang PF, Makawana JA, Wang ZC, Wang ZN, Yan-Gu, Jiang AQ, Zhu HL.
Abstract : A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.
|
Antibacterial activity against Bacillus thuringiensis after 24 hrs by MTT method
|
Bacillus thuringiensis
|
9.5
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.
Year : 2014
Volume : 24
Issue : 22
First Page : 2579
Last Page : 2583
Authors : Qin YJ, Wang PF, Makawana JA, Wang ZC, Wang ZN, Yan-Gu, Jiang AQ, Zhu HL.
Abstract : A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.
|
Antibacterial activity against Bacillus subtilis after 24 hrs by MTT method
|
Bacillus subtilis
|
8.9
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.
Year : 2014
Volume : 24
Issue : 22
First Page : 2579
Last Page : 2583
Authors : Qin YJ, Wang PF, Makawana JA, Wang ZC, Wang ZN, Yan-Gu, Jiang AQ, Zhu HL.
Abstract : A series of metronidazole-thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.
|
Antibacterial activity against Escherichia coli NCIM 2688 after 8 hrs
|
Escherichia coli
|
0.13
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1776
Last Page : 1783
Authors : Desai NC, Somani H, Trivedi A, Bhatt K, Nawale L, Khedkar VM, Jha PC, Sarkar D.
Abstract : A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.
|
Antibacterial activity against Pseudomonas fluorescens NCIM 2036 after 8 hrs
|
Pseudomonas fluorescens
|
0.014
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1776
Last Page : 1783
Authors : Desai NC, Somani H, Trivedi A, Bhatt K, Nawale L, Khedkar VM, Jha PC, Sarkar D.
Abstract : A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.
|
Antibacterial activity against Staphylococcus aureus NCIM 2010 after 12 hrs
|
Staphylococcus aureus
|
30.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1776
Last Page : 1783
Authors : Desai NC, Somani H, Trivedi A, Bhatt K, Nawale L, Khedkar VM, Jha PC, Sarkar D.
Abstract : A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.
|
Antibacterial activity against Bacillus subtilis NCIM 2079 after 12 hrs
|
Bacillus subtilis
|
0.37
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1776
Last Page : 1783
Authors : Desai NC, Somani H, Trivedi A, Bhatt K, Nawale L, Khedkar VM, Jha PC, Sarkar D.
Abstract : A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.
|
Antibacterial activity against Escherichia coli after 18 hrs by broth dilution method
|
Escherichia coli
|
1.62
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1704
Last Page : 1708
Authors : Subhedar DD, Shaikh MH, Arkile MA, Yeware A, Sarkar D, Shingate BB.
Abstract : We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116.
|
Antibacterial activity against Pseudomonas after 18 hrs by broth dilution method
|
Pseudomonas
|
0.49
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1704
Last Page : 1708
Authors : Subhedar DD, Shaikh MH, Arkile MA, Yeware A, Sarkar D, Shingate BB.
Abstract : We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116.
|
Antibacterial activity against Staphylococcus aureus after 18 hrs by broth dilution method
|
Staphylococcus aureus
|
30.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1704
Last Page : 1708
Authors : Subhedar DD, Shaikh MH, Arkile MA, Yeware A, Sarkar D, Shingate BB.
Abstract : We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116.
|
Antibacterial activity against Bacillus subtilis after 18 hrs by broth dilution method
|
Bacillus subtilis
|
1.35
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.
Year : 2016
Volume : 26
Issue : 7
First Page : 1704
Last Page : 1708
Authors : Subhedar DD, Shaikh MH, Arkile MA, Yeware A, Sarkar D, Shingate BB.
Abstract : We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116.
|
Inhibition of protein translation in Escherichia coli S30 cell extract using circular DNA with pBESTluc after 60 mins
|
Escherichia coli
|
30.0
nM
|
|
Journal : Bioorg Med Chem
Title : Covalently linked kanamycin - Ciprofloxacin hybrid antibiotics as a tool to fight bacterial resistance.
Year : 2017
Volume : 25
Issue : 11
First Page : 2917
Last Page : 2925
Authors : Shavit M, Pokrovskaya V, Belakhov V, Baasov T.
Abstract : To address the growing problem of antibiotic resistance, a set of 12 hybrid compounds that covalently link fluoroquinolone (ciprofloxacin) and aminoglycoside (kanamycin A) antibiotics were synthesized, and their activity was determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The hybrids were antagonistic relative to the ciprofloxacin, but were substantially more potent than the parent kanamycin against Gram-negative bacteria, and overcame most dominant resistance mechanisms to aminoglycosides. Selected hybrids were 42-640 fold poorer inhibitors of bacterial protein synthesis than the parent kanamycin, while they displayed similar inhibitory activity to that of ciprofloxacin against DNA gyrase and topoisomerase IV enzymes. The hybrids showed significant delay of resistance development in both E. coli and B. subtilis in comparison to that of component drugs alone or their 1:1 mixture. More generally, the data suggest that an antagonistic combination of aminoglycoside-fluoroquinolone hybrids can lead to new compounds that slowdown/prevent the emergence of resistance.
|
Antifungal activity against Cryptococcus neoformans after 96 hrs by broth micro-dilution method
|
Cryptococcus neoformans
|
7.8
ug.mL-1
|
|
Journal : J Nat Prod
Title : Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T.
Year : 2017
Volume : 80
Issue : 2
First Page : 565
Last Page : 568
Authors : Hara S, Ishikawa N, Hara Y, Nehira T, Sakai K, Gonoi T, Ishibashi M.
Abstract : Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 μg/mL, respectively.
|
Antifungal activity against Aspergillus niger after 96 hrs by broth micro-dilution method
|
Aspergillus niger
|
31.3
ug.mL-1
|
|
Journal : J Nat Prod
Title : Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T.
Year : 2017
Volume : 80
Issue : 2
First Page : 565
Last Page : 568
Authors : Hara S, Ishikawa N, Hara Y, Nehira T, Sakai K, Gonoi T, Ishibashi M.
Abstract : Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 μg/mL, respectively.
|
Antifungal activity against Candida albicans after 48 hrs by broth micro-dilution method
|
Candida albicans
|
62.5
ug.mL-1
|
|
Journal : J Nat Prod
Title : Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T.
Year : 2017
Volume : 80
Issue : 2
First Page : 565
Last Page : 568
Authors : Hara S, Ishikawa N, Hara Y, Nehira T, Sakai K, Gonoi T, Ishibashi M.
Abstract : Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 μg/mL, respectively.
|
Antifungal activity against Trichophyton mentagrophytes after 96 hrs by broth micro-dilution method
|
Trichophyton mentagrophytes
|
7.8
ug.mL-1
|
|
Journal : J Nat Prod
Title : Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T.
Year : 2017
Volume : 80
Issue : 2
First Page : 565
Last Page : 568
Authors : Hara S, Ishikawa N, Hara Y, Nehira T, Sakai K, Gonoi T, Ishibashi M.
Abstract : Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 μg/mL, respectively.
|
Antibacterial activity against Escherichia coli NCIM 2688 after 8 hrs by serial dilution method
|
Escherichia coli
|
162.0
nM
|
|
Journal : Eur J Med Chem
Title : Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life.
Year : 2018
Volume : 152
First Page : 358
Last Page : 369
Authors : Bhosle GS, Nawale L, Yeware AM, Sarkar D, Fernandes M.
Abstract : Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
|
Antibacterial activity against Pseudomonas aeruginosa NCIM 2036 after 8 hrs by serial dilution method
|
Pseudomonas aeruginosa
|
49.0
nM
|
|
Journal : Eur J Med Chem
Title : Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life.
Year : 2018
Volume : 152
First Page : 358
Last Page : 369
Authors : Bhosle GS, Nawale L, Yeware AM, Sarkar D, Fernandes M.
Abstract : Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
|
Antibacterial activity against Bacillus subtilis NCIM 2079 after 12 hrs by serial dilution method
|
Bacillus subtilis
|
135.0
nM
|
|
Journal : Eur J Med Chem
Title : Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life.
Year : 2018
Volume : 152
First Page : 358
Last Page : 369
Authors : Bhosle GS, Nawale L, Yeware AM, Sarkar D, Fernandes M.
Abstract : Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
|
Antibacterial activity against Staphylococcus aureus NCIM 2010 after 12 hrs by serial dilution method
|
Staphylococcus aureus
|
300.0
nM
|
|
Journal : Eur J Med Chem
Title : Antibacterial and anti-TB tat-peptidomimetics with improved efficacy and half-life.
Year : 2018
Volume : 152
First Page : 358
Last Page : 369
Authors : Bhosle GS, Nawale L, Yeware AM, Sarkar D, Fernandes M.
Abstract : Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid. The introduction of the non-natural amino acids of the study in the Tat peptide analogues results in increased resistance to degradation by proteolysis, significantly increasing their half-life. The peptides appear to inhibit bacteria by a membrane disruption mechanism, and have only a low cytotoxic effect on mammalian cells.
|
Binding affinity to biotinylated pre-miRNA-21 (unknown origin) by SPR analysis
|
Not specified
|
100.0
nM
|
|
Journal : ACS Med Chem Lett
Title : Tetracyclines as Inhibitors of Pre-microRNA Maturation: A Disconnection between RNA Binding and Inhibition.
Year : 2019
Volume : 10
Issue : 5
First Page : 816
Last Page : 821
Authors : Garner AL, Lorenz DA, Sandoval J, Gallagher EE, Kerk SA, Kaur T, Menon A.
Abstract : In a high-throughput screening campaign, we recently discovered the rRNA-binding tetracyclines, methacycline and meclocycline, as inhibitors of Dicer-mediated processing of microRNAs. Herein, we describe our biophysical and biochemical characterization of these compounds. Interestingly, although direct, albeit weak, binding to the pre-microRNA hairpins was observed, the inhibitory activity of these compounds was not due to RNA binding. Through additional biochemical and chemical studies, we revealed that metal chelation likely plays a principle role in their mechanism of inhibition. By exploring the activity of other known RNA-binding scaffolds, we identified additional disconnections between direct RNA interaction and inhibition of Dicer processing. Thus, the results presented within provide a valuable case study in the complexities of targeting RNA with small molecules, particularly with weak binding and potentially promiscuous scaffolds.
|
Binding affinity to 16S rRNA A-site in Escherichia coli S30 extract assessed as inhibition of translation measured after 30 mins by coupled transcription/translation-based luciferase reporter gene assay
|
Escherichia coli
|
100.0
nM
|
|
Journal : J Med Chem
Title : Effects of 5-O-Ribosylation of Aminoglycosides on Antimicrobial Activity and Selective Perturbation of Bacterial Translation.
Year : 2016
Volume : 59
Issue : 17
First Page : 8008
Last Page : 8018
Authors : Herzog IM, Louzoun Zada S, Fridman M.
Abstract : We studied six pairs of aminoglycosides and their corresponding ribosylated derivatives synthesized by attaching a β-O-linked ribofuranose to the 5-OH of the deoxystreptamine ring of the parent pseudo-oligosaccharide antibiotic. Ribosylation of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside kanamycin B led to improved selectivity for inhibition of prokaryotic relative to cytosolic eukaryotic in vitro translation. For the pseudodisaccharide aminoglycoside scaffolds neamine and nebramine, ribosylated derivatives were both more potent antimicrobials and more selective to inhibition of prokaryotic translation. On the basis of the results of this study, we suggest that modification of the 5-OH position of the streptamine ring of other natural or semisynthetic pseudodisaccharide aminoglycoside scaffolds containing an equatorial amine at the 2' sugar position with a β-O-linked ribofuranose is a promising avenue for the development of novel aminoglycoside antibiotics with improved efficacy and reduced toxicity.
|
Displacement of F-neo from premature miRNA21 (unknown origin) at 100 nM by fluorescence assay relative to control
|
Not specified
|
100.0
%
|
|
Journal : MedChemComm
Title : Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated interference in miR-21 biogenesis reverts epithelial to mesenchymal transition
Year : 2018
Volume : 9
Issue : 7.0
First Page : 1147
Last Page : 1154
Authors : Ghosh, Arpita, Degyatoreva, Natalya, Kukielski, Casey, Story, Sandra, Bhaduri, Sayantan, Maiti, Krishnagopal, Nahar, Smita, Ray, Arjun, Arya, Dev P., Maiti, Souvik
Abstract : Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose cell polarity and cellaEuro"cell adhesion and gain migratory and invasive properties to become mesenchymal cells that are very vital for development, wound healing and stem cell behavior and contribute pathologically to fibrosis and cancer progression. miR21, a potent regulator of the tumor suppressor gene PTEN, can be silenced to reverse EMT, thereby providing an attractive target for abrogating the malignant behavior of breast cancer. Here, we report the design, synthesis and binding of a peptidic-aminoglycoside (PA) based chemical library against pre-miR21 that led to the identification of a group of small molecules that bind to pre-miR21 with high affinities and antagonize miR-21 maturation and function, thereby reversing EMT. The approach described here offers a promising miRNA targeting platform where such aminosugar conjugates can be similarly used to target other oncogenic miRNAs. Minor changes in the amino acid sequence allow us to tailor the binding effectiveness and downstream biological effects, thus making this approach a potentially tunable method of regulation of miRNA function.
