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

作者：Galar Shadia A^*; Abdelsamie Ahmed S; Soliman Salwa M; Mortier Jeremie; Wolber Gerhard; Ali Mamdouh M; Tokuda Harukuni; Suzuki Nobutaka; Lida Akira; Ramadan Raghda A; El Diwani Hotta I

来源：European Journal of Medicinal Chemistry, 2013, 69: 115-124.

DOI：10.1016/j.ejmech.2013.07.049

• Synthesis
• Quinoxalines
• Epstein-Barr virus
• Cancer chemopreventive activity
• Docking
• Protein tyrosine kinase

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.

• 出版日期2013-11