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Chinese Journal of Organic Chemistry >

2014 , Vol. 34 >Issue 9: 1870 - 1874

DOI: https://doi.org/10.6023/cjoc201404036

Synthesis of Novel 17-[3,6-Dioxa-8-N-(substituted cinnamyol)- octanediamino]-17-demethoxygeldanamycin Derivatives

  • Wu Yunfei ,
  • Li Zhenyu ,
  • Wang Zhen ,
  • Xu Hongjiao ,
  • Wu Xingkang ,
  • Lu Chunhua ,
  • Shen Yuemao
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  • Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012

Received date: 2014-04-03

  Revised date: 2014-05-13

  Online published: 2014-06-09

Supported by

Project supported by the National Basic Research Program (973 Program, No. 2010CB833802), the National Natural Science Foundation of China (Nos. 81373304, 91313303), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT13028) and the National Science Found for Distinguished Young Scholars of China (No. 30325044).

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Abstract

Twenty six new 17-[3,6-dioxa-8-N-(substituted cinnamyol)octanediamino]-17-demethoxygeldanamycins were designed, synthesized and evaluated for their cytotoxicities against the growth of human breast cancer cell line MDA-MB-231 and binding affinities to heat shock protein 90 (Hsp90). Among these derivatives, 17-(3,6-dioxa-8-N-((E)-3-(3,5-dimethoxy- phenyl)acrylamido)octanediamino)-17-demethoxygeldanamycin (3u), was identified as the most potent one (IC50=1.5 μmol/L, Kd=1.14 μmol/L). Additionally, influence of substitutions at the cinnamyol group on the bioactivities of this type of Geldanamycin (GA) derivatives was discussed. This study was anticipated to provide reference for the further structure modifications of GA for developing antitumor agents.

Key words： heat shock protein 90 (Hsp90); geldanamycin (GA); synthesis; derivatives; antitumor activity

Cite this article

Wu Yunfei , Li Zhenyu , Wang Zhen , Xu Hongjiao , Wu Xingkang , Lu Chunhua , Shen Yuemao . Synthesis of Novel 17-[3,6-Dioxa-8-N-(substituted cinnamyol)- octanediamino]-17-demethoxygeldanamycin Derivatives[J]. Chinese Journal of Organic Chemistry, 2014 , 34(9) : 1870 -1874 . DOI: 10.6023/cjoc201404036

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