Design of New Thiosemicarbazone and Their Corresponding Acetylthiazole Composite as Anticancer Agent: In silico Approach DFT, Molecular Docking, and POM Analysis as Sustainable Development: Identification of Pharmacophore Sites

This study presents the design and synthesis of novel derivatives of Thiosemicarbazone (OS1) and its corresponding compound, Acetylthiazole (OS2), to evaluate their potential as effective anticancer agents. The compounds were characterized using FT-IR and 1H-NMR spectroscopy to confirm structural integrity and identify functional groups. The initial assessment of biological activity was based on in-silico studies, including DFT (Density Functional Theory) to examine the electronic stability of the compounds, as well as molecular docking analysis targeting liver cancer-associated proteins. The compounds demonstrated strong binding affinities to the active sites, indicating their potential therapeutic effects, and pharmacokinetic properties were further evaluated using POM analysis. An MTT assay was conducted on the human hepatocellular carcinoma cell line HepG2 to assess cytotoxicity. The results indicated that both compounds exhibited significant cytotoxic activity, with OS1 (IC50) = 66.98 µg/mL and OS2 (IC50) = 56.82 µg/mL), with OS2 being more effective in inhibiting cancer cells. To elucidate the mechanism of action at the molecular level, gene expression analysis of the TP53 gene was performed, and it was observed that OS2 enhanced the expression of this gene, which is associated with the regulation of programmed cell death (apoptosis). Based on these findings, we conclude that OS1 and OS2 possess promising pharmacological properties, and OS2 is a strong candidate for dual anticancer/antifungal drug development, which encourages further biological and clinical studies to fully evaluate its potential.