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

doi:10.6023/cjoc201404036

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

17-[3,6-二氧杂-8-N-(取代肉桂酰基)辛二胺]-17-去甲氧基格尔德霉素新颖衍生物的合成

吴云飞, 李震宇, 王贞, 徐洪蛟, 武兴康, 鲁春华, 沈月毛

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 E-mail:yshen@sdu.edu.cn
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

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).

1. Synthesis of Novel 17-[3,6-Dioxa-8-N-(substituted cinnamyol)- octanediamino]-17-demethoxygeldanamycin Derivatives.PDF(2717KB)

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]. Chin. J. Org. Chem., 2014, 34(9): 1870-1874.

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17-[3,6-二氧杂-8-N-(取代肉桂酰基)辛二胺]-17-去甲氧基格尔德霉素新颖衍生物的合成

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

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