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.

Graphical Abstract

Keywords:

• ADME properties
• carboxamide
• docking study
• MTT assay
• 1,2,3-triazole

Acknowledgments

The author is thankful to Post Graduate and Research Centre, Maulana Azad College Aurangabad, 431001, India for providing laboratory facility and Navin Fluorine International Limited, Dewas, Madhya Pradesh, 455001, India for the analytical support and encouragement for the higher study and authors also thankful to Tata Memorial Centre-Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) Kharghar, Navi Mumbai for In-vitro anti-cancer activity.

Disclosure statement

No potential conflict of interest was reported by the author(s).