Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF-7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by2-2,2-3,2-16and3-2was determined. The results showed: (1) among all compounds examined,2-16showed the highest antitumor activity and a broader spectrum of activity, with IC50values ranging from 1–2 µM; (2) their solubility was obviously improved; (3)2-3,2-16and3-2had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.Keywords:N13-substituted evodiamine derivatives;antitumor activity;apoptosis;solubility