Inhibitory Effects of Caffeic Acid Phenethyl Ester Derivatives on Replication of Hepatitis C Virus

被引:36
作者
Shen, Hui [1 ]
Yamashita, Atsuya [1 ]
Nakakoshi, Masamichi [2 ]
Yokoe, Hiromasa [3 ]
Sudo, Masashi [3 ]
Kasai, Hirotake [1 ]
Tanaka, Tomohisa [1 ]
Fujimoto, Yuusuke [1 ]
Ikeda, Masanori [4 ]
Kato, Nobuyuki [4 ]
Sakamoto, Naoya [5 ]
Shindo, Hiroko [6 ]
Maekawa, Shinya [6 ]
Enomoto, Nobuyuki [6 ]
Tsubuki, Masayoshi [3 ]
Moriishi, Kohji [1 ]
机构
[1] Univ Yamanashi, Grad Sch Med & Engn, Dept Microbiol, Div Med, Yamanashi, Japan
[2] Toho Univ, Fac Pharmaceut Sci, Chiba 2748510, Japan
[3] Hoshi Univ, Inst Med Chem, Tokyo 142, Japan
[4] Okayama Univ, Grad Sch Med Dent, Dept Tumor Virol, Okayama 7008530, Japan
[5] Hokkaido Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Sapporo, Hokkaido, Japan
[6] Univ Yamanashi, Fac Med, Dept Internal Med 1, Yamanashi, Japan
关键词
IN-VITRO; ANALOGS; CAPE; SUPPRESSION; ACTIVATION; EXPRESSION; CULTURE; GENOME; POTENT;
D O I
10.1371/journal.pone.0082299
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu 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 EC50 value of 1.0 mu 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.
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页数:11
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