2. Academic Validation
  3. Synthesis and biological evaluation of 3,5-disubstituted-4-alkynylisoxozales as a novel class of HSP90 inhibitors

Synthesis and biological evaluation of 3,5-disubstituted-4-alkynylisoxozales as a novel class of HSP90 inhibitors

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3129-34. doi: 10.1016/j.bmcl.2015.06.009.
Jian Sun 1,  Cai Lin 2,  Xiaochu Qin 2,  Xiaoping Dong 1,  Zhengchao Tu 2,  Fei Tang 2,  Chaonan Chen 3,  Jiancun Zhang 4
Affiliations

Affiliations

  • 1 Chengdu University of TCM, 37 Shierqiao Road, Chengdu 610075, China.
  • 2 Guangzhou Institutes of Biomedicine and Heath, Chinese Academy of Science, 190 Kaiyuan Road, Guangzhou 510530, China.
  • 3 Guangzhou Institutes of Biomedicine and Heath, Chinese Academy of Science, 190 Kaiyuan Road, Guangzhou 510530, China. Electronic address: [email protected].
  • 4 Guangzhou Institutes of Biomedicine and Heath, Chinese Academy of Science, 190 Kaiyuan Road, Guangzhou 510530, China; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedical and Heath, Chinese Academy Of Science, 190 Kaiyuan Road, Guangzhou 510530, China. Electronic address: [email protected].
PMID: 26112442 DOI: 10.1016/j.bmcl.2015.06.009
Abstract

A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)-copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various Cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90α and HSP90β comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human Cancer cell lines.

Keywords

3,5-Disubstitute-4-alkynylisoxazole; HSP90; HSP90 inhibitor.

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