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

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.National Natural Science Foundation of China [81560560]; Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs [K20160209]; Yunnan Basic Research Project [14051789]SCI(E)ARTICLE81322-13283