Lycorine-derived phenanthridine downregulators of host Hsc70 as potential hepatitis C virus inhibitors

被引：40

作者：

Chen, Duozhi ^{[1
]}

Cai, Jieyun ^{[1
]}

Yin, Junlin ^{[1
]}

Jiang, Jiandong ^{[2
]}

Jing, Chenxu ^{[1
,3
]}

Zhu, Yanping ^{[2
]}

Cheng, Junjun ^{[4
]}

Di, Yingtong ^{[1
]}

Zhang, Yu ^{[1
]}

Cao, Mingming ^{[1
]}

Li, Shunlin ^{[1
]}

Peng, Zonggen ^{[2
]}

Hao, Xiaojiang ^{[1
]}

机构：

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

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

[3] Yunnan Univ Tradit Chinese Med, Coll Tradit Chinese Med, Kunming 650500, Yunnan, Peoples R China

[4] Chinese Acad Med Sci, Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing 100050, Peoples R China

来源：

FUTURE MEDICINAL CHEMISTRY | 2015年 / 7卷 / 05期

基金：

中国国家自然科学基金;

关键词：

RESISTANCE; PROGRESS;

D O I：

10.4155/fmc.15.14

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：

Background: A new series of potential phenanthridine hepatitis C virus (HCV) inhibitors which work by suppressing Hsc70 expression in the host cell was designed and synthesized from lycorine. Results: Thirty-one new potential phenanthridine HCV inhibitors were synthesized and five of these compounds exhibited good anti-HCV activity and these inhibitors probably inhibit HCV by downregulating the host Hsc70 expression. Structure-activity analysis of these compounds revealed that the double bond between C-11 and C-12 and the substituents at C-8 and C-9 are important for their activity against HCV. Conclusion: Suppression of Hsc70 expression in the host cell to limit HCV replication is a potential anti-HCV strategy. Phenanthridines are probably the HCV inhibitors with this mode of action.

引用

页码：561 / 570

页数：10

共 30 条

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