Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, (CNMR)-C-13, and (HNMR)-H-1,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 mu g/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Automated summary

In this study, triazole-based acetamides were synthesized by chemically modifying 2-(4-isobutylphenyl) propanoic acid. The target compounds were produced in good yields and their structures were confirmed by various physiochemical and spectroscopic methods. The anti-liver carcinoma effects of these compounds were investigated and compound 7f showed the highest anti-proliferative activity with low toxicity. Molecular docking revealed that compound 7f exhibited excellent binding affinities to c-kit tyrosine kinase and protein kinase B. Therefore, compound 7f is considered as a suitable drug candidate for the treatment of hepatocellular carcinoma.