Design, semi-synthesis and bioevaluation of koumine-like derivatives as potential antitumor agents and .

Five series of novel koumine-like compounds were designed, semi-synthesized and systematically evaluated for antitumor activities. All compounds were evaluated for antiproliferative activity against four human cancer cell lines, including HT-29, HCT-116, HCT-15 and Caco-2. Most compounds exhibited much higher antiproliferation activities (IC <10 μM) than koumine. Two selected compounds and showed comparable antitumor effects to 5-FU , as well as better safety profiles. Further studies suggested that and could arrest HT-29 cell cycle in G2 phase and raise reactive oxygen species level, thus inducing cell apoptosis related to Erk MAPK and NF-κB signaling pathways inhibition. These results will greatly promote the druggability study of these koumine-like compounds.