Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line
Naheed Akhter, Sidra Batool, Samreen Gul Khan, Nasır Rasool, Fozia Anjum, Azhar Rasul, Şevki Adem, Sadaf Mahmood, Azizur Rehman, Mehr un Nisa, Zainib Razzaq, Jørn B. Christensen, Mohammed A. S. Abourehab, Syed Adnan Alı Shah, Syahrul Imran
Abstract
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, 13CNMR, and 1HNMR,) 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 µg/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.