Design, Synthesis and Biological Evaluation of Pentacyclic Triterpene Dimers as HCV Entry Inhibitors  

作　　者：Lingkuan Meng Qi Wang Tao Tang Sulong Xiao Lihe Zhang Demin Zhou Fei Yu 

机构地区：[1]Medical Faculty of Kunming University of Science and Technology, Kunming, Yunnan 650500, China [2]State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

出　　处：《Chinese Journal of Chemistry》2017年第8期1322-1328,共7页中国化学（英文版）

基　　金：Acknowledgement This work was supported by the National Natural Science Foundation of China （No. 81560560）, Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs （No. K20160209） and Yunnan Basic Research Project （No. 14051789）.

摘　　要：A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.

关 键 词：pentacyclic triterpene echinocystic acid DIMER HCV entry inhibitor 

分 类 号：TQ25[化学工程—有机化工] TB333[一般工业技术—材料科学与工程]