Design, synthesis and structure–activity relationship of novel quinoxaline derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase receptor

• Synthesis of quinoxaline derivatives 1–20.
• Studying of the possible inhibitory effects of synthesized the quinoxalines on Epstein–Barr virus early antigen activation.
• Studying of the inhibition of human tyrosine kinase (TRK).
• Molecular docking study.

The cancer chemopreventive activity of quinoxaline derivatives 1–20 has been evaluated by studying the inhibitory effect on Epstein–Barr virus early antigen (EBV-EA) activation. The quinoxaline derivatives 1–20 showed inhibitory effect on EBV-EA activation without cytotoxicity on Raji cells. All compounds exhibited dose dependent inhibitory activities, most of them showed significant activity at 1000 mol ratio/12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 7 and 9 exhibited stronger inhibitory effects on the EBV-EA activation than that of the representative control, oleanolic acid, at the highest measured concentration. In addition, compounds 7–10 showed potent and selective inhibition of human tyrosine kinase (TRK) in liver cancer HepG2 and breast cancer MCF-7 cell lines similar to the positive control, doxorubicin.

The protein tyrosine kinase inhibition and molecular docking studies of new quinoxaline derivatives were performed in order to rationalize their studied chemopreventive activity.Figure optionsDownload as PowerPoint slide