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

Investigational New Drugs volume 30, pages 164–175 (2012)Cite this article

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)-1H-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 G2/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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Acknowledgements

This study was supported by Grants BP-090-PP01, BP-090-CF03 and BP-091-CF03 of The National Health Research Institutes, Zhunan, Miaoli, Taiwan, R.O.C.

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Affiliations

  1. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053, Taiwan

    Wen-Tai Li, Der-Ren Hwang, Jen-Shin Song, Ching-Ping Chen, Tung-Wei Chen, Jiunn-Jye Chuu, Tzu-Wen Lien, Tsu-An Hsu, Chen-Lung Huang, Huan-Yi Tseng, Chu-Chung Lin, Heng-Liang Lin, Chung-Ming Chang, Yu-Sheng Chao & Chiung-Tong Chen

  2. Institute of Biophotonics, National Yang Ming University, Shih-Pai, Taipei, 11221, Taiwan

    Tung-Wei Chen & Chi-Hung Lin

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  1. Wen-Tai Li
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Correspondence to Chiung-Tong Chen.

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Li, WT., Hwang, DR., Song, JS. et al. Synthesis and biological evaluation of 2-amino-1-thiazolyl imidazoles as orally active anticancer agents. Invest New Drugs 30, 164–175 (2012). https://doi.org/10.1007/s10637-010-9547-7

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  • DOI: https://doi.org/10.1007/s10637-010-9547-7

Keywords

  • Microtubule
  • Cell cycle arrest
  • Apoptosis
  • Cytotoxicity
  • Orally active cancer therapeutics
  • Leukemia