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


CONCLUSIONS
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.
State Key Laboratory of Phytochemistry & Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
Duozhi
D
Chen
Jieyun
J
Cai
Junlin
J
Yin
Jiandong
J
Jiang
Chenxu
C
Jing
Yanping
Y
Zhu
Junjun
J
Cheng
Yingtong
Y
Di
Yu
Y
Zhang
Mingming
M
Cao
Shunlin
S
Li
Zonggen
Z
Peng
Xiaojiang
X
Hao
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006801:Humans; D010617:Phenanthridines / Q000737:chemistry* / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D047151:Amaryllidaceae Alkaloids; D000998:Antiviral Agents; D050883:HSC70 Heat-Shock Proteins; D010617:Phenanthridines; C015330:lycorine