Synthesis and Biological Evaluation of Furanoallocolchicinoids

Synthesis and Biological Evaluation of Furanoallocolchicinoids

A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell l...

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Bibliographic Details
Published in:Journal of medicinal chemistry Vol. 58; no. 2; pp. 692 - 704
Main Authors: Voitovich, Yuliya V, Shegravina, Ekaterina S, Sitnikov, Nikolay S, Faerman, Vladimir I, Fokin, Valery V, Schmalz, Hans-Gunther, Combes, Sebastien, Allegro, Diane, Barbier, Pascal, Beletskaya, Irina P, Svirshchevskaya, Elena V, Fedorov, Alexey Yu
Format: Journal Article
Language:English
Published: United States American Chemical Society 22-01-2015
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Line, Tumor
Cellular Biology
Colchicine - analogs & derivatives
Colchicine - pharmacology
Furans - chemical synthesis
Furans - pharmacology
Humans
Life Sciences
Mice
Mice, Inbred C57BL
Microtubules - drug effects
Models, Molecular
Structure-Activity Relationship
Tubulin Modulators - chemical synthesis
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Summary:A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell lines (AsPC-1, HEK293, and Jurkat) as well as against Wnt-1 related murine epithelial cell line W1308. The results of in vitro experiments demonstrated that the major effect of these compounds was the induction of cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding. In vivo testing of the most potent furanoallocolchicinoid 10c using C57BL/6 mice inoculated with Wnt-1 tumor cells indicated significant inhibition of the tumor growth.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm501678w