Design, synthesis, and molecular docking studies of novel quinoxaline derivatives as anticancer agents.

As lung cancer was placed foremost part among other types of cancer in terms of mortality. Recent researches are widely focused on developing multi-targeted and site-specific targeted drug designs. In the present study, we designed and developed a series of quinoxaline pharmacophore derivatives as active EGFR inhibitors for the treatment of non-small cell lung cancer. The compounds were synthesized through a condensation reaction between hexane-3,4-dione and methyl 3,4-diaminobenzoate as a first step. Their structures were confirmed by H-NMR, C-NMR, and HRMS spectroscopic methods. Cytotoxicity (MTT) were applied to determine anticancer activity of the compounds against breast (MCF7), fibroblast (NIH3 T3), and lung (A549) cell lines as EGFR inhibitors. Doxorubicin was used as a reference agent, compound 4i exhibited a significant effect among other derivatives with IC  = 3.902 ± 0.098 μM value against A549 cell line. The docking study showed that the best position on EGFR receptor could be observed with 4i. From the obtained evaluations of the designed series, compound 4i was a promising agent as EGFR inhibitor for further investigation and evaluation studies in the future.