Evaluation of anti-HCV activity and SAR study of (+)-lycoricidine through targeting of host heat-stress cognate 70 (Hsc70)

被引：26

作者：

Chen, Duo-Zhi ^{[1
,2
,3
,4
]}

Jiang, Jian-Dong ^{[5
]}

Zhang, Ke-Qing ^{[3
,4
]}

He, Hong-Ping ^{[1
]}

Di, Ying-Tong ^{[1
]}

Zhang, Yu ^{[1
]}

Cai, Jie-Yun ^{[1
,2
]}

Wang, Lei ^{[1
,2
]}

Li, Shun-Lin ^{[1
]}

Yi, Ping ^{[6
]}

Peng, Zong-Gen ^{[5
]}

Hao, Xiao-Jiang ^{[1
]}

机构：

[1] Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100039, Peoples R China

[3] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Minist Educ, Kunming 650091, Yunnan, Peoples R China

[4] Yunnan Univ, Key Lab Microbial Div Southwest China, Minist Educ, Kunming 650091, Yunnan, Peoples R China

[5] Chinese Acad Med Sci, Peking Union Med Coll, Lab Antiviral Res, Inst Med Biotechnol, Beijing 100050, Peoples R China

[6] Honghe Univ, Sch Sci, Key Lab Nat Pharmaceut & Chem Biol Yunnan Prov, Mengzi 661100, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 09期

基金：

中国国家自然科学基金;

关键词：

(+)-Lycoricidine; Heat-stress cognate 70 (Hsc70); Down-regulators; Structure-activity relationship (SAR); Anti-HCV activity; CHEMICAL-CONSTITUENTS; AMARYLLIDACEAE;

D O I：

10.1016/j.bmcl.2013.02.089

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The anti hepatitis C virus (HCV) activity of (+)-lycoricidine (1) was evaluated for the first time in this letter, yielding an EC50 value of 0.55 nmol/mL and an selection index (SI) value of 12.72. Further studies indicated that 1 induced this effect by down-regulating host heat-stress cognate 70 (Hsc70) expression. In addition, 20 derivatives were designed and synthesised to investigate the basic structure-activity relationship (SAR) of the title compound. Several of these derivatives exhibit a good inhibition of HCV, such as compound 3 (EC50 = 0.68 nmol/mL, SI = 33.86), compound 2d (EC50 = 15 nmol/mL, SI = 12) and compound 5 (EC50 = 33 nmol/mL, SI > 10.91). Meanwhile, the experimental data suggest that the modification of certain groups of (+)-lycoricidine can reduce the cytotoxicity of the compounds. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2679 / 2682

页数：4

共 22 条

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Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus [J].