Synthesis, In silico studies and antitumor activity of new 4-bromo-2-(1H-1,2,4-triazol-3-yl)aniline derived schiff bases

Abstract

In the present study, in an effort to develop an effective anticancer agents, novel series of Schiff bases derived from 4‑bromo‑2-(1H-1,2,4-triazol-3-yl) aniline have been synthesized and assessed for their anticancer activity in vitro, alongside in silico evaluations of pharmacokinetic properties. The new compounds (6a–j) were characterized using IR, NMR, spectroscopic and mass techniques. Among all, compound 6c exhibited superior efficacy compared to Doxorubicin in the treatment of MiaPaca2, and A549 with IC₅₀ values of 6.74 ± 0.21 µM and 2.86± 0.11 µM respectively. Also compound 6c showed good activity on HeLa and HCT116 cells with the IC₅₀ values 5.42 ± 0.35 µM and 7.37 ± 0.25 µM respectively. Furthermore, compound 6g also demonstrated anticancer activity against HeLa, A549, and HCT116, with IC₅₀ values of 14.35 ± 0.33 µM, 18.04 ± 0.41 µM, and 28.91 ± 0.79 µM. The insilico studies revealed that compounds showed an appropriate pharmacokinetic profile and favorable drug-likeness characteristics. Molecular docking and MD simulation studies against a set of EGFR and HER2 proteins reveals that compound 6c showed good docking energy and 100 ns MD simulation confirms that compound is stable inside the active site of EGFR. So, it can be concluded that 1,2,4-triazole based Schiff bases (6c and 6g) could serve as promising candidates for further development as novel promising bioactive molecules targeting EGFR.