Optical evodiamine derivatives: Asymmetric synthesis and antitumor activity

Abstract

Abstract 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.