Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (9): 1870-1874.DOI: 10.6023/cjoc201404036 Previous Articles     Next Articles


吴云飞, 李震宇, 王贞, 徐洪蛟, 武兴康, 鲁春华, 沈月毛   

  1. 山东大学药学院, 天然产物化学教育部重点实验室, 济南 250012
  • 收稿日期:2014-04-03 修回日期:2014-05-13 发布日期:2014-06-09
  • 通讯作者: 沈月毛
  • 基金资助:

    国家基础研究计划(973 项目, No. 2010CB833802)、国家自然科学基金(Nos. 81373304, 91313303)、长江学者和创新团队发展计划(No. IRT13028)和国 家杰出青年科学基金(No. 30325044)资助项目.

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   

  1. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012
  • Received:2014-04-03 Revised:2014-05-13 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).

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