title: Synthesis and biological evaluation of furanoallocolchicinoids.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Nizhny Novgorod State University , Gagarina av. 23, Nizhny Novgorod 603950, Russian Federation.
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Voitovich
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Shegravina
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Sitnikov
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Faerman
authors.forename: Valery V
authors.initials: VV
authors.lastname: Fokin
authors.forename: Hans-Gunther
authors.initials: HG
authors.lastname: Schmalz
authors.forename: Sebastien
authors.initials: S
authors.lastname: Combes
authors.forename: Diane
authors.initials: D
authors.lastname: Allegro
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbier
authors.forename: Irina P
authors.initials: IP
authors.lastname: Beletskaya
authors.forename: Elena V
authors.initials: EV
authors.lastname: Svirshchevskaya
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Fedorov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D050257:Tubulin Modulators; C032782:allocolchicine; D003078:Colchicine