Antimitotic Compounds

About

Technology: Compounds that inhibit cell proliferation are potentially useful in treating cancer, among other diseases. Curacin A is one such compound that inhibits cell growth and mitosis. Curacin A is believed to act by inhibiting microtubule processes associated with cell replication. It does this by binding to the colchicine-binding site, which is a relatively unique drug binding site.  The present invention provides an efficient synthetic strategy for the preparation of analogs that incorporate important structural elements of the marine natural product curacin A, the compositions and various uses of the compositions. The most active of these compounds at nanomolar concentrations inhibit tubulin polymerization, show growth inhibition activity, inhibited colchicines binding to tubulin and block mitotic progression. The compounds of the present invention represent some of the most potent synthetic curacin A analogs synthesized, with an activity profile rivaling that of the natural product despite the simplified structure, greater water solubility, and increased chemical stability.