Antibacterial activity of some 1,2,3,4-tetrasubstituted pyrrole derivatives and molecular docking studies (original) (raw)
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Synthesis, docking and biological evaluation of pyrrole-2-carbohydrazide derivatives
In the present study, a novel series of Pyrrole -2- carbohydrazide derivatives were synthesized and docking study was performed to rationalize the possible interactions between the synthesized compounds and active site. Pyrrole - 2- carbohydrazide derivatives were designed as Enoyl-acyl carrier protein reductase inhibitors. All compounds were screened for antimycobacterial activity against M.tuberculosis H37Rv using Microplate Alamar Blue Assay. Pyrazinamide (PZA) and Streptomycin were employed as the reference antimycobacterial agents. Among the series GS4 found to be most potent
European Journal of Medicinal Chemistry, 2019
Antibiotic resistance represents a major threat worldwide. Gram-positive and Gram-negative opportunistic pathogens are becoming resistant to all known drugs mainly because of the overuse and misuse of these medications and the lack of new antibiotic development by the pharmaceutical industry. There is an urgent need to discover structurally innovative antibacterial agents for which no pre-existing resistance is known. This work describes the identification, synthesis and biological evaluation of a novel series of 1,5-diphenylpyrrole compounds active against a panel of ESKAPE bacteria. The new compounds show high activity against both wild type and drug-resistant Gram+ve and Gram-ve pathogens at concentrations similar or lower than levofloxacin. Microbiology studies revealed that the plausible target of the pyrrole derivatives is the bacterial DNA gyrase, with the pyrrole derivatives displaying similar inhibitory activity to levofloxacin against the wild type enzyme and retaining activity against the fluoroquinoloneresistant enzyme.
Biotechnology and Bioprocessing, 2021
Background: Pyrimidine molecules' biological and chemotherapeutic importance in the medicinal world has been overlooked in many reports. We have previously synthesized new series of pyrrolo [3,2-d]pyrimidine derivatives (4a-4f) and here, we evaluate the antibacterial activity of these derivatives against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Salmonella bacteria. Materials and Methods: The agar well diffusion and agar dilution methods were used for determining inhibition zone diameter and minimum inhibitory concentration during preliminary evaluation of antimicrobial activity against gram-positive and gram-negative bacteria. Statistical analysis using Microsoft Excel 2010 was based on three independent experiments and the results were expressed as mean. Results: Some of the synthesized compounds exhibited antibacterial activity against the tested bacteria. Conclusion: Our findings indicate the antibacterial potential of the six novel synthetic pyrrol...
Journal of Saudi Chemical Society, 2014
In continuation of our research on nitrogen containing heterocyclic compounds to develop potent antimicrobial and antimycobacterial agents, some novel 2(3H) pyrrolone derivatives were synthesized. We report here two new series of 3-Arylidene-5-(4-chloro/methyl phenyl)-2(3H) pyrrolones (14-19) and 3-Arylidene-5-(4-chloro/methyl phenyl)-1-benzyl-2(3H) pyrrolones (20-25) prepared by reacting intermediate furanone compounds (6-13) with ammonia gas and benzylamine respectively. The structures of the title compounds were established on the basis of IR, 1 H NMR, mass spectral data and elemental analysis results. All the synthesized pyrrolone derivatives were evaluated for their possible antibacterial, antifungal and antitubercular activities. Among all the synthesized compounds, compound 17, 3-(4-Hydroxy-3-methoxybenzylidene)-5-(4-chlorophenyl)-2(3H)-pyrrolone, emerged as a lead compound exhibiting the highest antibacterial, antifungal and antitubercular activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Mycobacterium tuberculosis with 6.25 lg/mL MIC (minimum *
Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity
Bioorganic & Medicinal Chemistry, 2008
Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for eighteen polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of αβ-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r 2 of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2carboxylic acid ethyl ester) is the most stable. These results illuminate the binding process and should be valuable in the design of new pyrrole-based colchicine site inhibitors as these compounds have very accessible syntheses.
Synthesis, characterization and biological activity of novel pyrrole compounds
5-((1, 3-dioxoisoindolin-2-yl) methyl-2-hydroxybenzohydrazide (1) undergoes facile condensation with aromatic aldehydes to afford the corresponding N'-Substitutedphenyl-5-((1, 3-dioxoisoindolin-2-yl) methyl)-2-hydroxy benzo hydrazides (2a-h) in good yield. Cyclocondensation of compounds (2a-h) with maleic anhydride yields 1-(5-((1, 3dioxoisoindolin-2-yl) methyl)-2-hydroxybenzamido) -5-oxo-2-substituted phenyl-2, 5-dihydro-1H-pyrrole-3carboxylic acid (3a-h). The structures of these compounds were established on the basis of analytical and spectral data. All the newly synthesized compounds were evaluated for their antibacterial and antifungal activities.
Design and Synthesis of Diverse Pyrrole-2-carboxamide Derivatives as a Potent Antibacterial Agents
Journal of Heterocyclic Chemistry, 2017
A series of pyrrole-2-carboxamide derivatives (4a-j) were synthesized and evaluated for theirantibacterial activity. Among the tested compounds, the most effective were 4a, 4b, 4c, 4d, 4e, 4g and 4h with MIC value in the range of 1.05-12.01 μg/mL against Gram-positive and Gramnegativebacterial strains. Further, the synthesized compounds have been screened for their invitro antifungal activity. In the present study, design and expeditious synthesis of novel 1-(4-chlorobenzyl)-N-(4-methoxybenzyl)-1Hpyrrole-2-carboxamide hybrid molecules as promising antibacterial agents.
Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents
Journal of Enzyme Inhibition and Medicinal Chemistry
Pyrroles and its fused forms possess antimicrobial activities, they can easily interact with biomolecules of living systems. A series of substituted pyrroles, and its fused pyrimidines and triazines forms have been synthesised, all newly synthesised compound structures were confirmed by spectroscopic analysis. Generally, the compounds inhibited growth of some important human pathogens, the best effect was given by: 2a, 3c, 4d on Gram-positive bacteria and was higher on yeast (C. albicans), by 5c on Gramnegative bacteria and by 5a then 3c on filamentous fungi (A. fumigatus and F. oxysporum). Such results present good antibacterial and antifungal potential candidates to help overcome the global problem of antibiotic resistance and opportunistic infections outbreak. Compound 3c gave the best anti-phytopathogenic effect at a 50-fold lower concentration than Kocide 2000, introducing a safe commercial candidate for agricultural use. The effect of the compounds on DNA was monitored to detect the mode of action.
Molecules
The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a-m and carbohydrazide analogues 5a-l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.