Synthesis and anti-HCV entry activity studies of β-cyclodextrin-pentacyclic triterpene conjugates

Abstract

In our previous studies, oleanolic acid (OA) and echinocystic acid (EA), isolated from Dipsacus asperoides, were found to have anti-HCV entry properties. The major issue for members of this type of triterpene is their low water solubility. In this study, a series of new water-soluble triazole-bridged β-cyclodextrin (CD)-pentacyclic triterpene conjugates were synthesized via click chemistry. Thanks to the attached β-CD moiety, all synthesized conjugates showed lower hydrophobicity (Alog P) than their parent compounds. Several conjugates exhibited moderate anti-HCV entry activity. With the exception of per-O-methylated β-CD-pentacyclic triterpene conjugates, all other conjugates showed no cytotoxicity based on an alamarBlue assay carried out with HeLa, HepG2, MDCK, and 293T cells. More interestingly, the hemolytic activity of these conjugates disappeared upon the introduction of β-CDs. Easy access to such conjugates that combine the properties of β-CD and pentacyclic triterpenes may provide a way to obtain a new class of anti-HCV entry inhibitors.

Keywords: HCV entry inhibitors; antiviral agents; click chemistry; cyclodextrins; echinocystic acid; pentacyclic triterpenes.