Design, synthesis and molecular docking study of novel quinoxalin-2(1H)-ones as anti-tumor active agents with inhibition of tyrosine kinase receptor and studying their cyclooxygenase-2 activity

•Synthesis of new quinoxaline derivatives.•Studying of cytotoxic activity of synthesized the quinoxalines.•Studying of the inhibition of human tyrosine kinase (TRK) and cyclooxygenase-2 (COX-2).•Studying of molecular docking of active compounds.•Studying of structure activity relationship.

On continuation to our work, new quinoxalin-2(1H)-ones were synthesized to study their cytotoxic effect against HepG-2 and MCF-7 with their effect on the human tyrosine kinase (TRK). Compounds 12, 18, 15, 13, 11a, 20 and 16, respectively, were found to be more potent than cisplatin against HepG2 and selective to TRK. Also, compounds 12, 18, 20, 13, 14, and 22, respectively, exhibited decidedly activity against MCF-7 and selectivity against human TRK compared to cisplatin. A molecular docking study was also performed to gain comprehensive understanding into plausible binding modes and to conclude the structure activity relationships of the synthesized compounds. Moreover, anti-inflammatory activity was studied. Compounds 12, 15, 18 and 22 were found to be potent and selective against COX-2.

Graphical abstractQuinoxalin-2(1H)-ones were synthesized to test their antitumor activity and inhibition of TRK and to elucidate SAR by docking study with evaluation of their anti-inflammatory activity.Figure optionsDownload full-size imageDownload as PowerPoint slide