title: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191 (China). slxiao@bjmu.edu.cn.
authors.forename: Sulong
authors.initials: S
authors.lastname: Xiao
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Longlong
authors.initials: L
authors.lastname: Si
authors.forename: Yongying
authors.initials: Y
authors.lastname: Shi
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Li
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Chuanling
authors.initials: C
authors.lastname: Zhang
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
authors.forename: Demin
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D053978:Pentacyclic Triterpenes; D047392:beta-Cyclodextrins; C031215:betadex
keywords: HCV entry inhibitors; antiviral agents; click chemistry; cyclodextrins; echinocystic acid; pentacyclic triterpenes