Design, synthesis, cytotoxicity, and molecular docking studies of 1-(4-methoxyphenyl)-N-substituted phenyl-1H-1,2,3-triazole-4-carboxamide derivatives

Abstract

A new series of 1-(4-methoxyphenyl)-N-substituted phenyl-1H-1,2,3-triazole-4-carboxamide derivates (4A–4N) have been synthesized in excellent yields and structures were characterized by spectral techniques like 1H-NMR, 13C-NMR, LC-MS, and FT-IR. The newly synthesized derivatives were evaluated for anticancer activity against breast cancer cell lines MCF-7 and MDA-MB-231. Among them, compound 4H (IC50 = 13.11 and 23.61 μM) and compound 4M (IC50 = 11.55–31.87 μM) shows good cytotoxicity activity toward both cell line, while compounds 4B (IC50 = 9.48 μM), 4I (IC50 = 7.11 μM), and 4J (IC50 = 8.27 μM) showed promising cytotoxicity against MCF-7 cell line as compared with standard (Doxorubicin). Also explored docking study with binding mode of interactions and active site in EGFR tyrosinse (PDB ID: 2J5F) proteins and molecular docking study shows very good interaction with the tyrosine kinase active site. In addition to this targeted compounds were studied the pharmacokinetics and the compounds were follow Lipinski’s rule of five as well as compounds have acceptable good drug-likeness score properties.