title: Synthesis, biological evaluation and molecular modeling of 1,2,3-triazole analogs of combretastatin A-1.
abstract: The synthesis, cytotoxicity, inhibition of tubulin polymerization data and anti-angiogenetic effects of seven 1,5-disubstituted 1,2,3-triazole analogs and two 1,4-disubstituted 1,2,3-triazole analogs of combretastatin A-1 (1) are reported herein. The biological studies revealed that the 1,5-disubstituted 1,2,3-triazoles 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diol (6), 3-methoxy-6-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)benzene-1,2-diamine (8) and 5-(2,3-difluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (9) were the three most active compounds regarding inhibition of both tubulin polymerization and angiogenesis. Molecular modeling studies revealed that combretastatins 1 and 2 and analogs 5-11 could be successfully docked into the colchicine binding site of α,β-tubulin.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068, N-0316 Oslo, Norway.
authors.forename: Oyvind W
authors.initials: OW
authors.lastname: Akselsen
authors.forename: Kristin
authors.initials: K
authors.lastname: Odlo
authors.forename: Jing-Jy
authors.initials: JJ
authors.lastname: Cheng
authors.forename: Giorgio
authors.initials: G
authors.lastname: Maccari
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
authors.forename: Trond Vidar
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D058105:Polymerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013267:Stilbenes / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D014230:Triazoles; D014404:Tubulin; D050257:Tubulin Modulators; C063690:combretastatin A-1