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.
Yang
Baiyuan
B
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Zhu
Zhiqing C
ZC
Goodson
Holly V
HV
Miller
Marvin J
MJ
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