Anticancer, Antioxidant Activities and Molecular Docking Study of Thiazolidine -4-one and Thiadiazol Derivatives

Abstract: Liver cancer accounts for a major portion of the global cancer burden. In many nations, the prevalence of this condition has risen in recent decades. New series of thaiazolidinones and thaiadiazolidine have been designed, synthesized, and evaluated for potential antioxidant and antihepatocarcinogenic activity. The antioxidant activity of synthesized compounds was evaluated using a DPPH assay. Furthermore, we examined the compounds against HepG2 cells using MTT assay, flow cytometry analysis through the cell cycle, reactive oxygen species, and apoptosis. The result showed that compound 6b has the highest antioxidant activity with IC₅₀ =60.614±0.739 µM. The anticancer activity showed that compounds 5 and 6b have significant toxicity against liver cancer cells HepG2, IC50 values (9.082 and 4.712) µM, respectively. Flow cytometry experiments revealed that compound 5 arrested HepG2 cells in the S process, while compound 6b arrested HepG2 cells in the G1. Compound 6b had a greater reduction in reactive oxygen species and late apoptosis than compound 5. Substantially, compound 5 had affinity energies of -7.6 and -8.5 for Akt and CDK4 proteins, respectively, but compound 6b had affinity energies of -7.8 and -10.1 for Akt1 and CDK4 proteins, respectively. Consequently, compound 6b had lower binding energies than compound 5. In this work, we used multiple bioinformatics methods to shed light on the prospective therapeutic use of these series as novel candidates to target immune cells in the tumor microenvironment of hepatocellular carcinomas such as CD8+ T cells, endothelial cells, and hematopoietic stem cells. The results of antioxidant, anticancer, molecular docking studies, and bioinformatic analysis showed that compound 6b has a potential impact and could be developed for drug discovery with further research.