Stilbene derivatives that are colchicine-site microtubule inhibitors have antileukemic activity and minimal systemic toxicity

Stilbenes are a group of natural compounds with many biological activities. Two highly potent Stilbenes, cis-3,4',5-trimethoxy-3'-aminostilbene (stilbene 5c) and cis-3,4',5-trimethoxy-3'-hydroxystilbene (stilbene 6c) induce G2/M cell-cycle arrest and leukemic cell death in nanomolarity range without affecting normal bone marrow progenitor cells. The mechanism of Stilbenes is mediated by interfering with microtubule polymerization through the colchicine-binding site. Docking of the Stilbenes into tubulin structure confirms that Stilbenes fit into the colchicine-binding pocket. Animal studies show that Stilbenes are well tolerated in mice and are capable of inducing more than 50% leukemic cell death by a single dose injection. A 5-day treatment with low-dose Stilbenes suppresses tumor growth in mice with established tumor xenografts. No major organ damage was detected by histological section. Our results indicate that stilbene 5c is a microtubule-interfering agent and can be potentially useful in leukemic therapy.