Design, synthesis and molecular docking of 1,2,4-triazole schiff base hybrids as tubulin, EGFR inhibitors and apoptosis-inducers

Abstract

The corporate 1,2,4-triazole scaffold was used to synthesize new Schiff base compounds as anticancer agents against several cancer cell lines. Compounds 4d, 4e, and 4k exhibit strong anticancer activity, with IC50 values ranging from 6.78 to 23.03 µM. The inhibitory effects of compounds 4d, 4e, and 4k against EGFR kinase and tubulin were further investigated as they showed significant cytotoxic activity. Compound 4d showed excellent EGFR inhibitory efficacy at an IC50 value of 0.13 µM when compared to lapatinib (IC50 = 0.04 µM). Compound 4k also demonstrated 82.78% inhibition of β-tubulin at 25 μM compared to the untreated control. On the other hand, compound 4d also caused a total cell cycle arrest at the G1/S phase. Furthermore, compound 4d caused 5.28 percent necrosis in the K562 cell line and induced early rather than late apoptosis. A comprehensive molecular docking analysis was carried out to investigate the potential interactions and binding patterns of the three most active compounds, 4d, 4e, and 4k, within the active sites of the targeted EGFR kinase and tubulin polymerization.