title: Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus.
abstract: Caffeic acid phenethyl ester (CAPE) has been reported as a multifunctional compound. In this report, we tested the effect of CAPE and its derivatives on hepatitis C virus (HCV) replication in order to develop an effective anti-HCV compound. CAPE and CAPE derivatives exhibited anti-HCV activity against an HCV replicon cell line of genotype 1b with EC50 values in a range from 1.0 to 109.6 µM. Analyses of chemical structure and antiviral activity suggested that the length of the n-alkyl side chain and catechol moiety are responsible for the anti-HCV activity of these compounds. Caffeic acid n-octyl ester exhibited the highest anti-HCV activity among the tested derivatives with an EC50 value of 1.0 µM and an SI value of 63.1 by using the replicon cell line derived from genotype 1b strain Con1. Treatment with caffeic acid n-octyl ester inhibited HCV replication of genotype 2a at a similar level to that of genotype 1b irrespectively of interferon signaling. Caffeic acid n-octyl ester could synergistically enhance the anti-HCV activities of interferon-alpha 2b, daclatasvir, and VX-222, but neither telaprevir nor danoprevir. These results suggest that caffeic acid n-octyl ester is a potential candidate for novel anti-HCV chemotherapy drugs.
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakakoshi
authors.affiliation: Institute of Medical Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yokoe
authors.affiliation: Institute of Medical Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sudo
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Kasai
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shindo
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Maekawa
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.affiliation: Institute of Medical Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tsubuki
authors.affiliation: Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Moriishi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D002109:Caffeic Acids; D012367:RNA, Viral; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol