Thiazolidinone Derivatives: Synthesis, Characterization, Antimicrobial Evaluation, and Cytotoxicity Studies

Search of selective and novel antimicrobial compounds with a wider therapeutic window led us to design and synthesize a novel series of 2-[2-(1,3-substitutedphenylprop-2-enylidene)hydrazono]thiazolidin-4-ones derivatives. Ammonium acetate assisted cyclization of 1-(1,3-substitutedphenylallylidene)thiosemicarbazide (10-18) with ethylchloroacetate fetched a novel series of 2-[2-(1,3-substitutedphenylprop-2-enylidene)hydrazono]thiazolidin-4-ones derivatives (19-27). CHN analysis, Fourier-transform infrared, ¹H and ¹³C nuclear magnetic resonance, and electrospray ionization ESI-mass spectrometry spectral data elucidated and confirmed the chemical structures of the compounds. All the synthesized compounds (1-27) were explored for their effect on in vitro growth of pathogenic microorganisms by disc diffusion method. In vitro antimicrobial activity was performed against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. The minimum inhibitory concentration (MIC) was detected using the double dilution method. Results inferred that the compounds 18, 19, 21, 25, and 26 showed encouraging results, with good inhibition and low MIC value. To elucidate the antimicrobial mechanism of action of most potent compound (25), it was docked into the active site of two prominent antimicrobial targets. The molecular docking studies revealed that compound 25 is a E. coli FabH inhibitor. The cytotoxic activities of selected compounds on MCF-7 cell line showed that all the compounds offered more than 70% viability (IC₅₀ >200 µM) in the concentration range of 3.125-50 µM. Overall, it is concluded that compound 25 is a potential non-cytotoxic antibacterial lead compound having E. coli FabH inhibitory potential that can be further investigated to identify more potent chemotherapeutic agents.