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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Design, Synthesis, Docking and Biological Evaluation of Novel 4-hydroxy Coumarin Derivatives

Author(s): N. Ramalakshmi, S.R. Chitra*, P. Manimegalai and S. Arunkumar

Volume 17, Issue 2, 2021

Published on: 31 January, 2020

Page: [201 - 213] Pages: 13

DOI: 10.2174/1573409916666200131142619

Price: $65

Abstract

Background: Hospital-acquired (HA) infections are caused due to E. coli, which is resistant to multiple drugs particularly to fluoroquinolone class of drugs. Urinary tract infections (UTI) affects people in the community and hospitals. 150 million people per annum are suffering from UTI worldwide.

Methods: In this present study, we designed 36 novel coumarin derivatives, also we predicted pharmacokinetic and toxicity parameters. Docking studies were also carried out and all the compounds were evaluated for antibacterial activity against resistant quinolone E. coli strain ATCC 25922. It was interesting to note that the introduction of electron-withdrawing group on the aromatic ring resulted in compounds with an increased antibacterial activity, which is observed in compound 6 (with 4-nitro substitution), compound 23 (chloro) and compound 30 (chloro, nitro).

Results: From the MIC results, it was observed that compounds 6, 23 and 30 showed higher activity with 0.5μg/ml, 0. 12 μg/ml, 0.5 μg/ml respectively. Docking studies were performed with the active site of DNA gyrase (PDB ID: 4CKK). The maximum binding energy was found to be -10.7 Kcal/mol.

Conclusion: From the study, it was found that 3 compounds were potentially active against quinolone- resistant E. coli strains. This study can further be extended for in vivo evaluation.

Keywords: E. coli strains, coumarin derivatives, evaluation of novel 4-hydroxy, MIC results, DNA gyrase, toxicity parameters.

Graphical Abstract
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