title: Inhibitors and promoters of tubulin polymerization: synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents.
abstract: A series of dihalogenated chalcones and structurally related dienones were synthesized and evaluated for their antiproliferative activity in 10 different cancer cell lines and for their effect on microtubule assembly. All compounds showed cytotoxic activity, with IC(50) values in the 5-280 μM range depending on the chalcone structure and the cell line. Five of the compounds were found to be tubulin polymerization inhibitors. In contrast, one of the compounds was found to stabilize tubulin to the same extent as the anticancer drug docetaxel. Molecular modeling suggested that the tubulin inhibitors bind to the colchicine binding site of β-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site.
authors: Department of Chemistry, Medicinal Chemistry, University of Gothenburg, Göteborg, Sweden.
authors: Christine
authors: C
authors: Dyrager
authors: Malin
authors: M
authors: Wickström
authors: Maria
authors: M
authors: Fridén-Saxin
authors: Annika
authors: A
authors: Friberg
authors: Kristian
authors: K
authors: Dahlén
authors: Erik A A
authors: EA
authors: Wallén
authors: Joachim
authors: J
authors: Gullbo
authors: Morten
authors: M
authors: Grøtli
authors: Kristina
authors: K
authors: Luthman
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007659:Ketones; D058105:Polymerization; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000819:agonists / Q000187:drug effects*; D050257:Tubulin Modulators / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D007659:Ketones; D014404:Tubulin; D050257:Tubulin Modulators