Design, Synthesis, In Silico Studies, and Anticancer Activity of Novel Nitrobenzene Thiazolyl Hydrazones against the EGFR

Objective: Design, synthesis, characterization, and in silico studies of novel nitrobenzene thiazolyl hydrazones (VIa–VIh) and inhibitory action against the EGFR. Methods: All synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines in vitro utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and EGFR enzymatic assay. Target molecule features were investigated through a computational study that included drug-likeness, ADMET profiling, and molecular docking. Results and Discussion: The compounds (IVb), (IVe), and (IVh) showed prominent anticancer activity with an IC50 value of 15.45, 18.23, 10.69 μM, and 12.75, 16.05, 11.95 μM against chosen cancer cell lines A549, and MCF-7 respectively. Additionally, in vitro EGFR enzymatic activity provided insight into the process of anticancer action of the majority of the active molecules. According to a molecular docking study, every molecule binds to EGFR (PDB ID: 5D41) with high affinities. Conclusions: Among all, derivatives (IVb), (IVe), and (IVh) showed moderate inhibition compared to different tested derivatives. Thus, the present study of all novel nitrobenzene thiazolyl hydrazones could be further optimized to develop new EGFR inhibitors.