5-(4-(3-(substituted aryl/alkyl)-4-oxothiazolidin-2-yl)benzylidene)thiazolidine-2,4-dione molecules: Synthesis, Biological potential and in silico studies

Abstract

Abstract Background: A novel series of thiazolidine-2,4-dione molecules was derived and their chemical structures were established using physiochemical parameters and spectral techniques (1H-NMR, IR, MS etc.). The synthesized molecules were then evaluated for their antioxidant, anticancer and antimicrobial potential.Results and discussion: Serial tube dilution method was employed to evaluate the antimicrobial potential against selected fungal and bacterial strains by taking fluconazole and cefadroxil as reference antifungal and antibacterial drugs respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity was used to assess the antioxidant potential of the synthesized analogues. The interactions of the derived thiazolidine-2,4-dione analogues with DNA gyrase and CDK8 enzymes were explored using molecular docking studies. Further, anticancer potential of the best docked molecules was assessed using MTT assay. The drug likeness was also evaluated by studying different ADME parameters of the synthesized analogues.Conclusion: In antioxidant evaluation studies, the analogue H5 with IC50 = 14.85 μg/mL was found to be the most active molecule. The antimicrobial evaluation outcomes suggested that the molecules H5, H13, H15 and H18 possessed moderate to promising activity against the selected species of microbial strains having MIC range 7.3 µM to 26.3 µM. The molecular docking studies revealed molecules H18 (docking score = -4.07) and H7 (docking score = -3.77) have reasonably fair docking score in the binding site of DNA gyrase in comparison to the reference drug. The molecules H2 (docking score = -5.75) and H10 (docking score = -5.41) having good score, exhibited decent interaction in the binding pocket of CDK8. The ADME studies revealed that all the compounds found to be drug like.