Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3831-3. doi: 10.1016/j.bmcl.2010.03.056. Epub 2010 Mar 15.
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.
环-C 修饰的生物碱是通过亚胺硝酮 Diels-Alder 反应从秋水仙碱合成的，具有高度的区域和立体选择性。几种类似物表现出与秋水仙碱本身相似的细胞毒性活性，作为秋水仙碱的前药，通过在测定条件下的反 Diels-Alder 反应。体外微管聚合试验表明，这些修饰影响了它们与微管蛋白的相互作用。
