Development of bivalent oleanane-type triterpenes as potent HCV entry inhibitors

• A series of bivalent oleanane-type triterpenes were synthesized and the SAR of the anti-HCV entry activities were evaluated.
• The effects of the length, rigidity and hydrophobicity of the linker on the anti-HCV activities were studied.
• Several new bivalent EAs exert dramatically potent enhancement of inhibition with IC50 values at nM level.
• The hemolytic effect of the new derivatives was depleted.

The development of entry inhibitors is an emerging approach to the prevention and reduction of HCV infection. Starting from echinocystic acid (EA), a μM HCV entry inhibitor, we have developed a series of bivalent oleanane-type triterpenes which, upon optimization of the length, rigidity and hydrophobicity of the linker, exert dramatically potent enhancement of inhibition with IC50 values extending into the nM level. This study establishes the importance of triterpene natural products as new leads in the development of potential HCV entry inhibitors.

A series of bivalent oleanane-type triterpenes were found to exert high anti-HCV entry activities. The putative mechanism of bivalent EA derivatives on blocking virus entry is disruption of the interacting binding between HCV envelope E2 and its receptor CD81.Figure optionsDownload as PowerPoint slide