Is the Trimethoxy Motif Necessary for Inhibition of Tubulin Polymerization?
Amy M. Deveau1, E.M. Joshi2, R. Ravindra3, S. Bane3, and T.L. Macdonald2. (1) University of New England, Biddeford, ME, (2) University of Virginia, Charlottesville, VA, (3) State University of New York, Binghamton, NY The clinical success of Taxol and the promise of compounds like the combretastatins support the continued investigation of the a,b-tubulin heterodimer as a molecular target in cancer chemotherapy. Although colchicine remains the gold standard for probing tubulin structure, colchicine and its biaryl derivatives have not been thoroughly investigated for their anti-proliferative properties. In fact, 2-methoxy-5-(2,3,4-trimethoxyphenyl)cyclohepta-2,4,6-trien-1-one, the biaryl equivalent of colchicine, retains most of the anti-mitotic properties of colchicine itself. In this work, we investigated whether biaryl colchicinoids targeting the a,b-tubulin heterodimer may be viable agents for cancer chemotherapy. Towards further understanding of the SAR and therapeutic potential of
