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Title: Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus
Authors: Shen H. 
Yamashita A.
Nakakoshi M.
Yokoe H.
Sudo M.
Kasai H.
Tanaka T.
Fujimoto Y.
Ikeda M.
Kato N.
Sakamoto N.
Shindo H.
Maekawa S.
Enomoto N.
Tsubuki M.
Moriishi K.
Keywords: alpha2b interferon
antivirus agent
caffeic acid
caffeic acid methyl ester
caffeic acid n octyl ester
caffeic acid phenethyl ester
chlorogenic acid
cinnamic acid henethyl ester
dihydrocaffeic acid methyl ester
ferulic acid
rosmarinic acid
unclassified drug
antiviral activity
concentration (parameters)
concentration response
controlled study
drug efficacy
drug potentiation
Hepatitis C virus
Hepatitis C virus genotype 1
Hepatitis C virus genotype 2
intracellular signaling
median effective concentration
structure activity relation
virus inhibition
virus replication
Antiviral Agents
Caffeic Acids
Phenylethyl Alcohol
RNA, Viral
Structure-Activity Relationship
Virus Replication
Issue Date: 2013
Citation: Shen H., Yamashita A., Nakakoshi M., Yokoe H., Sudo M., Kasai H., Tanaka T., Fujimoto Y., Ikeda M., Kato N., Sakamoto N., Shindo H., Maekawa S., Enomoto N., Tsubuki M., Moriishi K. (2013). Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus. PLoS ONE 8 (12) : e82299. ScholarBank@NUS Repository.
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 EC 50 values in a range from 1.0 to 109.6 ?M. 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 EC 50 value of 1.0 ?M 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. © 2013 Shen et al.
Source Title: PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0082299
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