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

• Published in: Pharmaceuticals
• Main Author: Akhter N.; Batool S.; Khan S.G.; Rasool N.; Anjum F.; Rasul A.; Adem Ş.; Mahmood S.; Rehman A.U.; Nisa M.U.; Razzaq Z.; Christensen J.B.; Abourehab M.A.S.; Shah S.A.A.; Imran S.
• Format: Article
• Language: English
• Published: MDPI 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85148939350&doi=10.3390%2fph16020211&partnerID=40&md5=16314e1a09efb0f787aba49b8b12b31a

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. © 2023 by the authors.