2,3,5‐Trisubstituted Thiazolidinone Derivatives as Potential Antimicrobial and Antitubercular Agents and In Silico Studies

Author:

Nefisath P.12,Kumar Vasantha1,Shashiprabha 1,Patil Shashank M.3,Ramu Ramith3,S Shradha4,Dasappa Jagadeesh Prasad2ORCID

Affiliation:

1. Department of PG Studies and Research in Chemistry Sri Dharmasthala Manjunatheshwara College (Autonomous) Ujire 574240 India

2. Department of Studies in Chemistry Mangalore University Mangalagangothri 574199 India

3. Department of Biotechnology and Bioinformatics School of Life Sciences JSS Academy of Higher Education and Research Mysuru 570015 India

4. Department of PG Studies and Research in Biotechnology Sri Dharmasthala Manjunatheshwara College (Autonomous) Ujire 574240 India

Abstract

AbstractA series of novel 2,3,5‐trisubstituted thiazolidinone derivatives was designed and synthesized. Compounds were tested for their antimicrobial and antitubercular activities. Compounds 3‐(2,4‐difluorobenzyl)‐5‐[(5‐methylfuran‐2‐yl)methylidene]‐2‐(phenylimino)‐1,3‐thiazolidin‐4‐one (5 c) and 3‐(2,4‐difluorobenzyl)‐2‐((3‐fluorophenyl)imino)‐5‐((Z)‐4‐hydroxybenzylidene) thiazolidin‐4‐one (6 f) exhibited remarkable antimicrobial activity against Klebsiella pneumoniae and Escherichia coli respectively. All compounds except 3‐(2,4‐difluorobenzyl)‐5‐((3‐(4‐fluorophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)methylene)‐2‐(phenylimino)thiazolidin‐4‐one (5 a) and (6 f) exposed excellent antitubercular activity in comparison with the standard drugs against H37RV strain of Mycobacterium tuberculosis (ATCC No‐ 27294). In addition, molecular docking and dynamic simulations studies were performed with E. coli Mur B (EMB) (PDB ID: 2Q85), Aspergillus fumigatus sterol 14‐alpha demethylase (ASD) (PDB ID: 4UYM) and Mycobacterium tuberculosis pantothenate synthetase (MPS) (PDB ID: 3IVX) proteins against all compounds and the most potent compound (5 c) displayed higher binding proficiency. These compounds may serve as lead compounds for further optimization to achieve promising therapeutic properties.

Publisher

Wiley

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