7-Diethylamino-3(2'-benzoxazolyl)-coumarin is a novel microtubule inhibitor with antimitotic activity in multidrug resistant cancer cells.

Microtubules are a proven target for anticancer drug development because they are critical for mitotic spindle formation and the separation of chromosomes at mitosis. We here report a novel synthetic microtubule inhibitor 7-diethylamino-3(2'-benzoxazolyl)-coumarin (DBC). DBC causes destabilization of microtubules, leading to a cell cycle arrest at G(2)/M stage. In addition, human cancer cells are more sensitive to DBC (IC(50) 44.8-475.2nM) than human normal fibroblast (IC(50) 7.9microM), and DBC induces apoptotic cell death of cancer cells. Furthermore, our data show that DBC is a poor substrate of drug efflux pumps and effective against multidrug resistant (MDR) cancer cells. Taken together, these results describe a novel pharmacological property of DBC as a microtubule inhibitor, which may make it an attractive new agent for treatment of MDR cancer.