Ultrasound Assisted Synthesis and In Silico Modelling of 1,2,4-Triazole Coupled Acetamide Derivatives of 2-(4-Isobutyl phenyl)propanoic acid as Potential Anticancer Agents

Abstract

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 N-substituted 1,2,4-triazole-2-thiol derivatives. The target compounds 6a–f were efficiently synthesized in significant yields (75–89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid 1 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 6d containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC50 value of 13.004 µg/mL, while compound 6e showed the lowest potency with an IC50 value of 28.399 µg/mL. The order of anticancer activity was found to be: 6d > 6b > 6f > 6a > 6c > 6e, 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 6d showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest ∆G value of −176.152 kcal/mol. Compound 6d has been identified as a promising candidate for treatment of liver cancer.

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

“…It improves the solubility of the drug and its candidacy as a good drug molecule. Earlier, we reported the synthesis of various structural hybrids of oxadiazole-based acetamide [ 26 , 27 , 28 , 29 ], and it has been proven from the literature that heterocycle-based compounds possess good anti-cancer activity [ 30 ]. Thus, in an extension of our earlier research on heterocycles, –COOH group of 2-(4-isobutylphenyl)propanoic acid was cyclized into a 1,2,4-triazole ring 4.…”

New Acetamide Derivatives of the COX-II Inhibitors-A Brief Review

“…According to a brief review of the literature on the biological activities of acetamide derivatives, they have potent antimicrobial [10], anti-inflammatory [11], anti-tumor [12], anti-HIV [13], antiviral [14], anticonvulsant [15], analgesic [16], anti-cancer [17], anti-allergic [18], sedative-hypnotic [19], and antihypertensive [20]. The synthetic adaptability of quinazolinones, which enables the synthesis of a large number of structurally different derivatives, has further aided this wide range of biological functions [21].…”