1017402-17-3Relevant articles and documents
Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines
Demchuk, Dmitry V.,Samet, Alexander V.,Chernysheva, Natalia B.,Ushkarov, Vladimir I.,Stashina, Galina A.,Konyushkin, Leonid D.,Raihstat, Mikhail M.,Firgang, Sergei I.,Philchenkov, Alex A.,Zavelevich, Michael P.,Kuiava, Ludmila M.,Chekhun, Vasyl F.,Blokhin, Dmitry Yu.,Kiselyov, Alex S.,Semenova, Marina N.,Semenov, Victor V.
, p. 738 - 755 (2014/01/23)
A series of 1,5-diaryl- and 4,5-diaryl-1,2,3-triazole derivatives of combretastatin A4 were synthesized and evaluated as antimitotic microtubule destabilizing agents using the sea urchin embryo model. Structure-activity relationship studies identified compounds substituted with 3,4,5- trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of human cancer cell lines including multi-drug resistant cells. 4,5-Diaryl-1,2,3-triazoles (C-C geometry) were found to be considerably more active than the respective 1,5-diaryl-1,2,3-triazoles (N-C geometry). Compound 10ad′ induced G2/M cell cycle arrest and apoptosis in human T-leukemia Jurkat cells via caspase 2/3/9 activation and downregulation of the antiapoptotic protein XIAP. A mitotic catastrophe has been evaluated as another possible cell death mode.
