Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus.
Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus.
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DOI：
10.1371/journal.pone.0082299
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moriishi K
中科院分区：
文献类型：
--
作者：
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
咖啡酸苯乙酯（CAPE）是一种多功能化合物。在本报告中，我们测试了CAPE及其衍生物对丙型肝炎病毒（HCV）复制的影响，以开发一种有效的抗HCV化合物。CAPE及其衍生物对基因型为1b的HCV复制子细胞系具有抗HCV活性，EC50值在1.0 ~ 109.6µM之间。化学结构和抗病毒活性分析表明，这些化合物的抗hcv活性与正烷基侧链和儿茶酚部分的长度有关。咖啡酸正辛酯的抗hcv活性最高，EC50值为1.0µM， SI值为63.1。咖啡酸正辛酯对基因2a型和基因1b型丙型肝炎病毒复制的抑制水平与干扰素信号传导无关。咖啡酸正辛酯能协同增强干扰素- α 2b、daclatasvir和VX-222的抗hcv活性，而对telaprevir和danoprevir没有协同增强作用。这些结果提示咖啡酸正辛酯是新型抗hcv化疗药物的潜在候选者。
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.
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