title: Development of bivalent oleanane-type triterpenes as potent HCV entry inhibitors.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Medical Faculty of Kunming University of Science and Technology, Kunming 650500, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yongying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Si
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Lee
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: slxiao@bjmu.edu.cn.
authors.forename: Sulong
authors.initials: S
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Maorong
authors.initials: M
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Chuanling
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Hengli
authors.initials: H
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: deminzhou@bjmu.edu.cn.
authors.forename: Demin
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D014315:Triterpenes; C413246:oleanane; D009828:Oleanolic Acid
keywords: Dimer; Echinocystic acid; HCV entry inhibitor; Triterpene