PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties
Bhosale, J.D.; Dabur, R.; Jadhav, G.P.; Bendre, R.S. Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties. Molecules2018, 23, 875.
Bhosale, J.D.; Dabur, R.; Jadhav, G.P.; Bendre, R.S. Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties. Molecules 2018, 23, 875.
Bhosale, J.D.; Dabur, R.; Jadhav, G.P.; Bendre, R.S. Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties. Molecules2018, 23, 875.
Bhosale, J.D.; Dabur, R.; Jadhav, G.P.; Bendre, R.S. Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties. Molecules 2018, 23, 875.
Abstract
The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity 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 compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 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 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 to 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 existing antifungal compounds.
Keywords
carboxamide; carbohydrazine; antibacterial; antifungal; molecular docking; Schiff base; NMR; IR
Subject
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
7 March 2018
Commenter:
Sanjay Patil
The commenter has declared there is no conflict of interests.
Comment:
This article is very good article in the sense that, very simple chemical molecules which follow lipinski's rule of 5 and yet showing biological profile as antifungal.
Molecular docking studies support the hypothesis and elaborate on its mode of action with how toxicities of existing drugs can be reduced with compounds not interacting heme iron part os the enzyme.
Overall, very good work. Wish maximum citations
Commenter: Sanjay Patil
The commenter has declared there is no conflict of interests.
Molecular docking studies support the hypothesis and elaborate on its mode of action with how toxicities of existing drugs can be reduced with compounds not interacting heme iron part os the enzyme.
Overall, very good work. Wish maximum citations
Commenter: Satish Dumraliya
The commenter has declared there is no conflict of interests.