Syntheses and biological evaluation of ring-C modified colchicine analogs

  • Bioorg Med Chem Lett. 2010 Jun 15;20(12):3831-3. doi: 10.1016/j.bmcl.2010.03.056.
Baiyuan Yang  1 ,  Zhiqing C Zhu ,  Holly V Goodson ,  Marvin J Miller
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
PMID: 20529690 DOI: 10.1016/j.bmcl.2010.03.056
Abstract

Ring-C modified Alkaloids were synthesized from colchicine using iminonitroso Diels-Alder reactions in a highly regio- and stereoselective fashion. Several analogs exhibited cytotoxic activity similar to that of colchicine itself against PC-3 and MCF-7 Cancer cell lines, by serving as prodrugs of colchicine through retro Diels-Alder reactions under the assayed conditions. In vitro microtubule polymerization assays indicated that these modifications affected their interaction with tubulin.