Potential Fluorinated Anti‐MRSA Thiazolidinone Derivatives with Antibacterial, Antitubercular Activity and Molecular Docking Studies

Abstract MRSA infection is one of the alarming diseases in the current scenario. Identifying newer molecules to treat MRSA infection is of urgent need. In the present study, we have designed fluorinated thiazolidinone derivatives with various aryl/heteroaryl units at 5 th position of the thiazolidinone core as promising anti‐MRSA agents. All the compounds were screened for antibacterial activity against four bacterial strains. Among the tested compounds, the halogenated compounds with simple arylidene ring, (5 Z)‐5‐[(3‐chloro‐2‐fluorophenyl)methylidene]‐2‐[(1,3‐thiazol‐2‐yl)amino]‐1,3‐thiazol‐4(5 H)‐one (4b), (5 Z)‐5‐[(4‐chloro‐2‐fluorophenyl)methylidene]‐2‐[(1,3‐thiazol‐2‐yl)amino]‐1,3‐thiazol‐4(5 H)‐one (4c), (5 Z)‐5‐[(3‐fluoro‐4‐methylphenyl)methylidene]‐2‐[(1,3‐thiazol‐2‐yl)amino]‐1,3‐thiazol‐4(5 H)‐one (4f) and (5 Z)‐5‐[(3,5‐difluorophenyl)methylidene]‐2‐[(1,3‐thiazol‐2‐yl)amino]‐1,3‐thiazol‐4(5 H)‐one (4g) showed excellent activity with MIC 3.125–6.25 μg/mL against S. aureus and P. aeruginosa organism. Furthermore, these potent compounds were screened against MRSA strains, ESKAPE panel organism, and H37Rv mycobacterium strain. Compounds4c(MIC 0.39 μg/mL), and4f(MIC 0.39 and 0.79 μg/mL) displayed promising activity against MRSA strains (ATCC and clinical isolates, respectively). The most potent compounds,4c and4f eradicated the growth of bacterial colonies in a time‐kill assay indicated that these are bactericidal in nature. The preliminary toxicity study of the potent molecules revealed that these compounds are non‐hemolytic in nature as they did not induce lysis in human RBCs. In addition, the molecular docking and dynamics studies of compounds4b,4c,4f and4g were carried out on MurB protein of S. aureus(PDB code: 1HSK). Docking results demonstrated remarkable hydrogen bonding interaction with key amino acids ARG310, ASN83, GLY79 and π‐π interactions with TYR149 which confirm the mode of action of the molecules..

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:19
Enthalten in:	Chemistry & Biodiversity - 19(2022), 2

Beteiligte Personen:	Kumar, Vasantha [VerfasserIn] Shetty, Premalatha [VerfasserIn] H. S., Arunodaya [VerfasserIn] Chandra K., Sharath [VerfasserIn] Ramu, Ramith [VerfasserIn] Patil, Shashank M. [VerfasserIn] Baliga, Anuradha [VerfasserIn] Rai, Vaishali M. [VerfasserIn] M, Shalini Shenoy [VerfasserIn] Udupi, Vishwanatha [VerfasserIn] Poojary, Vishwanatha [VerfasserIn] Poojary, Boja [VerfasserIn]

BKL:	42.90 43.12

Anmerkungen:	© 2022 Wiley‐VHCA AG, Zurich, Switzerland

Umfang:	17

doi:	10.1002/cbdv.202100532

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	WLY003121569