Structure-Activity Relationships of Terpendole E and Its Natural Derivatives

Terpendole E (TerE) is the first natural product that inhibits mitotic kinesin Eg5 (kinesin spindle protein). Recently, TerE is suggested to have a different binding site and/or inhibitory mechanism than other L5 loop-binding type Eg5 inhibitors. Here, we report the structure-activity relationships (SARs) of natural TerE derivatives, including two compounds not reported before. Our SAR results indicated that the paspaline-like indolediterpene skeleton is important for Eg5 inhibition, and that both further oxidation except for 11-position and further prenylation decreases the Eg5 inhibitory activity.