Syntheses and biological evaluation of ring-C modified colchicine analogs.
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.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Baiyuan
B
Yang
Zhiqing C
ZC
Zhu
Holly V
HV
Goodson
Marvin J
MJ
Miller
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D003603:Cytotoxins; D006801:Humans; D011355:Prodrugs; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects
D000970:Antineoplastic Agents; D003603:Cytotoxins; D011355:Prodrugs; D014404:Tubulin; D003078:Colchicine