Abstract
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.
Acknowledgements
We thank W Wang (Kunming Institute of Botany, Chinese Academy of Sciences, China) for providing help with purifying the compounds used in this study.
Financial & competing interests disclosure
This research was financially supported by the National Natural Science Foundation of China (81402828 and 21432010) and the “Xi Bu Zhi Guang” Foundation of The Chinese Academy of Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.