Inhibitors and promoters of tubulin polymerization: Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents
2011 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 19, no 8, 2659-2665 p.Article in journal (Refereed) Published
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 IC50 values in the 5-280 mu M 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 beta-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site.
Place, publisher, year, edition, pages
2011. Vol. 19, no 8, 2659-2665 p.
Chalcones, Cytotoxicity, Tubulin polymerization, Molecular modeling
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-152919DOI: 10.1016/j.bmc.2011.03.005ISI: 000289281600019PubMedID: 21459004OAI: oai:DiVA.org:uu-152919DiVA: diva2:414422