Synthesis of N-(5,7-diamino-3-phenyl-quinoxalin-2-yl)-3,4,5-substituted anilines and N-[4[(5,7-diamino-3-phenylquinoxalin-2-yl)amino]benzoyl]-l-glutamic acid diethyl ester: Evaluation of in vitro anti-cancer and anti-folate activities

Several diamino quinoxalines were designed, synthesized and evaluated as anti-tumor agents. Two compounds showed the most potent cytotoxic activities against the leukemia CCRF-CEM cell line (GI50 < 0.01 μM) and the ovarian cancer cell line OVCAR-4 (GI50 = 0.03 μM), respectively, with comparable/better activities than Methotrexate (MTX). Docking calculations of the complexes of hDHFR with the most active compounds identified the binding mode of the described molecules with respect to MTX.

Several 5,7-diamino-3-phenylquinoxaline derivatives were designed, synthesized and evaluated as anti-tumor agents. Their anti-folate activity and DHFR-inhibitors interaction models are presented here.Figure optionsDownload as PowerPoint slide