TY - JOUR

T1 - Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line

AU - Akhter, Naheed

AU - Batool, Sidra

AU - Khan, Samreen Gul

AU - Rasool, Nasir

AU - Anjum, Fozia

AU - Rasul, Azhar

AU - Adem, Sevki

AU - Mahmood, Sadaf

AU - Rehman, Aziz ur

AU - Nisa, Mehr un

AU - Razzaq, Zainib

AU - Christensen, Jorn B.

AU - Abourehab, Mohammed A. S.

AU - Shah, Syed Adnan Ali

AU - Imran, Syahrul

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - 2-(4-isobutylphenyl) propanoic acid

KW - hepatocellular carcinoma

KW - anti-cancer

KW - 1

KW - 2

KW - 4-triazole

KW - molecular docking

KW - acetamides

KW - BIOLOGICAL EVALUATION

KW - TRIAZOLE DERIVATIVES

KW - DESIGN

KW - INHIBITOR

KW - DISCOVERY

U2 - 10.3390/ph16020211

DO - 10.3390/ph16020211

M3 - Journal article

C2 - 37259360

VL - 16

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 2

M1 - 211

ER -