Synthesis and biological evaluation of paclitaxel-thiocolchicine hybrids.

The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was surprisingly devoid of tubulin activity, acting on a distinct and yet to identify molecular target.