Find in Library

The development of an economical method for the synthesis of biologically active compounds was the major goal of this research. In the present study, we have reported the ultrasound-radiation-assisted synthesis of a series of novel <i>N-</i>substituted 1,2,4-triazole-2-thiol derivatives. The target compounds <b>6a–f</b> were efficiently synthesized in significant yields (75–89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid <b>1</b> with different electrophiles using ultrasound radiation under different temperatures. The sonication process accelerated the rate of the reaction as well as yielded all derivatives compared to conventional methods. All derivatives were confirmed by spectroscopic (FTIR, ¹HNMR, ¹³CNMR, HRMS) and physiochemical methods. All derivatives were further screened for their anticancer effects against the HepG2 cell line. Compound <b>6d</b> containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC₅₀ value of 13.004 µg/mL, while compound <b>6e</b> showed the lowest potency with an IC₅₀ value of 28.399 µg/mL. The order of anticancer activity was found to be: <b>6d</b> > <b>6b</b> > <b>6f</b> > <b>6a</b> > <b>6c</b> > <b>6e</b>, respectively. The in silico modelling of all derivatives was performed against five different protein targets and the results were consistent with the biological activities. Ligand <b>6d</b> showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest ∆G value of −176.152 kcal/mol. Compound <b>6d</b> has been identified as a promising candidate for treatment of liver cancer.