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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 |
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Main Authors: | , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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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. |
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ISSN: | 0167-6997 1573-0646 |
DOI: | 10.1007/s10637-010-9547-7 |