Synthesis, molecular modeling and biological evaluation of cinnamic acid derivatives with pyrazole moieties as novel anticancer agents

Abstract

A series of pyrazole derivatives (1e–30e) has been designed and synthesized, and their biological activities were evaluated for EGFR and HER-2 inhibition and tumor cell antiproliferation. Among the compounds synthesized, compound 30e exhibited excellent enzyme inhibitory activity (IC₅₀ = 0.21 ± 0.05 μM for EGFR and IC₅₀ = 1.08 ± 0.15 μM for HER-2). Compound 30e also showed the most potent antiproliferative activity, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC₅₀ values of 0.30 ± 0.04 and 0.44 ± 0.05 μM, respectively. The molecular docking study was performed to analyze the probable binding models and the 3D-QSAR models were built for the rational design of EGFR/HER-2 inhibitors. Based on the results obtained, compound 30e with potent EGFR and HER-2 inhibitory activity may be a potential anticancer agent.