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Lycorine-derived phenanthridine downregulators of host Hsc70 as potential hepatitis C virus inhibitors
Duozhi Chen1, Jieyun Cai, Junlin Yin
1State Key Laboratory of Phytochemistry & Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
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.
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