1,5-Disubstituted 1,2,3-triazoles as cis-restricted analogues of combretastatin A-4: Synthesis, molecular modeling and evaluation as cytotoxic agents and inhibitors of tubulin
- 作者：Kristin Odlo ; Jean Hentzen ; Jé ; ré ; mie Fournier dit Chabert ; Sylvie Ducki ; Osman A.B.S.M. Gani ; Ingebrigt Sylte ; Martina Skrede ; Vivi Ann Flø ; renes ; Trond Vidar Hansen
- 关键词：Combretastatin A-4 ; Cytotoxic ; 1 ; 2 ; 3-Triazoles ; Molecular modeling
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：1 May 2008
- 卷：16
- 期：9
- 页码：4829-4838
- 文件大小：585 K
摘要
A series of cis-restricted 1,5-disubstituted 1,2,3-triazole analogues of combretastatin A-4 (1) have been prepared. The triazole 12f, 2-methoxy-5-(1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-5-yl)aniline, displayed potent cytotoxic activity against several cancer cell lines with IC50 values in the nanomolar range. The ability of triazoles to inhibit tubulin polymerization has been evaluated, and 12f inhibited tubulin polymerization with IC50 = 4.8 μM. Molecular modeling experiments involving 12f and the colchicine binding site of 
alpha" title="greek small letter alpha" border="0">,β-tubulin showed that the triazole moiety interacts with β-tubulin via hydrogen bonding with several amino acids.
alpha" title="greek small letter alpha" border="0">,β-tubulin showed that the triazole moiety interacts with β-tubulin via hydrogen bonding with several amino acids.