Abstract
Aims and Objective:
The infectious disease treatment remains a challenging concern
owing to the increasing number of pathogenic microorganisms associated with resistance to
multiple drugs. A promising approach for combating microbial infection is to combine two or more
known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis
and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents
were dissimilated.
Materials and Methods:
The preparation of the substituted 5-benzylidene-2-thiazolyimino-4-
thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds
have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi
strains. Minimum inhibitory concentration and minimum bacterial concentration were both
determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery
Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the
title compounds.
Results:
PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone
hybrids. All tested compounds were found to kill and to inhibit the growth of a vast
variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin,
ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective
molecular target identification and revealed favorable interaction with the target enzymes E. coli
MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active
compounds was found toxic.
Conclusion:
Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable
antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and
may find a potential therapeutic use to eradicate infectious diseases.