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Synthesis and biological evaluation of 2-amino-1-thiazolyl imidazoles as orally active anticancer agents

Summary Designed from a high throughput screened hit compound, novel 2-amino-1-thiazolyl imidazoles were synthesized and demonstrated cytotoxicity against human cancer cells. 1-(4-Phenylthiazol-2-yl)-4-(thiophen-2-yl)-1 H -imidazol-2-amine (compound 2 ), a 2-amino-1-thiazolyl imidazole, inhibited tu...

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Published in:Investigational new drugs 2012-02, Vol.30 (1), p.164-175
Main Authors: Li, Wen-Tai, Hwang, Der-Ren, Song, Jen-Shin, Chen, Ching-Ping, Chen, Tung-Wei, Lin, Chi-Hung, Chuu, Jiunn-Jye, Lien, Tzu-Wen, Hsu, Tsu-An, Huang, Chen-Lung, Tseng, Huan-Yi, Lin, Chu-Chung, Lin, Heng-Liang, Chang, Chung-Ming, Chao, Yu-Sheng, Chen, Chiung-Tong
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Language:English
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Summary:Summary Designed from a high throughput screened hit compound, novel 2-amino-1-thiazolyl imidazoles were synthesized and demonstrated cytotoxicity against human cancer cells. 1-(4-Phenylthiazol-2-yl)-4-(thiophen-2-yl)-1 H -imidazol-2-amine (compound 2 ), a 2-amino-1-thiazolyl imidazole, inhibited tubulin polymerization, interacted with the colchicine-binding sites of tubulins, and caused cell cycle arrest at the G 2 /M phase in human gastric cancer cells. Disruption of the microtubule structure in cancer cells by compound 2 was also observed. Compound 2 concentration-dependently inhibited the proliferation of cancer cells in histocultured human gastric and colorectal tumors. Given orally, compound 2 prolonged the lifespans of leukemia mice intraperitoneally inoculated with the murine P388 leukemic cells. We report 2-amino-1-thiazolyl imidazoles as a novel class of orally active microtubule-destabilizing anticancer agents.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-010-9547-7