Synthesis, Biological Evaluation and <i>In Silico</i> Studies of Some 2‐Substituted Benzoxazole Derivatives as Potential Anticancer Agents to Breast Cancer

Abstract

Abstract In an attempt to develop potent and selective anticancer agents, some 5‐ or 6‐ and N‐substituted benzoxazol‐2‐carboxamide derivatives were designed, synthesized, and evaluated for their cyclooxygenase inhibitory, antioxidant, and anti‐proliferative activity against MCF‐7 and MDA‐MB‐231 cell lines. Among them 5‐OMe, N‐piperidine substituted (compound 30 ), 5‐OMe, N‐4‐methylpiperidine substituted (compound 31 ) and 5‐Cl, N‐piperidine substituted (compound 34 ) benzoxazole 2‐carboxamide compounds have a moderate inhibitory effect in COX‐1 and COX‐2 enzymes. Anti‐proliferative studies show that compound 30 (IC 50 =5.35 μM) and compound 31 (IC 50 =5.82 μM) have similar activity to reference drug 5‐FU (IC 50 =3.95 μM) on MCF‐7 cell but they have lower toxic effect for healthy WI‐38 cell line. For the MCF‐7 cell line, compounds 30 and 31 show approximately 1.5 times higher selectivity compared to the 5‐FU control. Among the synthesized compounds 30 , 31 , and 34 had the best anti‐proliferative effect and were used to perform flow cytometry and cell cycle analysis on MCF‐7 cell line. To predict the binding modes and pharmacokinetic parameters of all compounds, in silico studies were carried out. These compounds may shed light on cancer treatment and cancer research.