Optical evodiamine derivatives: Asymmetric synthesis and antitumor activity

Evodiamine and its derivatives have an asymmetric center at the C13b position. Herein, isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis. Their inhibitory activities toward topoisomerases I and II and their cytotoxicities in cancer cell lines were evaluated. All the four isomers exhibited good to excellent antitumor potency and the (S)-isomers were generally more active than the (R)-isomers. The binding modes of (S)-2 with topoisomerases I and II were also clarified by molecular docking.

Graphical abstractIsomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis and their antitumor activity was investigated. All the four isomers exhibited good to excellent antitumor potency.Figure optionsDownload full-size imageDownload as PowerPoint slide