Synthesis, biological evaluation and in-silico ADME studies of novel series of thiazolidin-2,4-dione derivatives as antimicrobial, antioxidant and anticancer agents

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 molecule 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. Further, the anticancer potential of the selected molecules was assessed against DU-145 cancer cell lines using MTT assay. The drug-likeness was also evaluated by studying in-silico 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 results of anticancer evaluation revealed that all the screened derivatives possess mild anticancer potential. The in-silico ADME studies revealed that all the compounds were found to be drug-like.

Keywords: ADME; Anticancer; Antimicrobial; Antioxidant; Characterization; Synthesis.

Scheme 1

Synthesis of 5-(-4-(3-(substituted aryl/alkyl)-4-oxothiazolidin-2-yl)benzylidene) thiazolidine-2,4-dione derivatives (H1–H19)

Fig. 1

Antibacterial evaluation results against Gram positive species using cefadroxil as standard drug

Fig. 2

Antibacterial evaluation results against Gram negative species using cefadroxil as standard drug

Fig. 3

Antifungal evaluation results against fungal species using fluconazole as standard drug

Fig. 4

Antioxidant screening of synthesized compounds using ascorbic acid as standard drug

Fig. 5

Anticancer evaluation results of compounds H2, H10 and H11 against DU-145 prostate cancer cell lines

Fig. 6

Structure activity relationship of synthesized compounds