Synthesis of the analogs of plocabulin and their preliminary structure-activity relationship study.

Plocabulin, a marine natural polyketide isolated from the sponge Lithoplocamia lithistoides, is a novel and potent microtubule-destabilizing agent. Guided by the reported binding mode, several new analogs of plocabulin have been designed through removing the right aliphatic chain and further modifying on the carbamate group and the enamide unit. The preliminary results indicate that the right aliphatic chain in plocabulin is allowed to remove with a little loss of activity, the carbamate group plays a role in the activity, and particularly, the enamide unit has an important effect on the activity. This new finding will aid the design of novel potent tubulin-binding agents based on plocabulin.