Lycorine-derived phenanthridine downregulators of host Hsc70 as potential hepatitis C virus inhibitors
Lycorine-derived phenanthridine downregulators of host Hsc70 as potential hepatitis C virus inhibitors
复制标题
石蒜碱衍生的菲啶下调宿主 Hsc70 作为潜在的丙型肝炎病毒抑制剂
DOI：
10.4155/fmc.15.14
复制
发表时间：
2015-01-01
影响因子：
4.2
通讯作者：
Hao, Xiaojiang
中科院分区：
文献类型：
--
作者：
Chen, Duozhi;Cai, Jieyun;Hao, Xiaojiang
背景资料：以石蒜碱为起始原料，设计合成了一系列通过抑制Hsc 70在宿主细胞中的表达而发挥作用的菲啶类丙型肝炎病毒（HCV）抑制剂。结果如下：合成了31个新的菲啶类HCV抑制剂，其中5个化合物表现出良好的抗HCV活性，这些抑制剂可能通过下调宿主Hsc 70的表达来抑制HCV。构效关系分析表明，C-11和C-12之间的双键以及C-8和C-9上的取代基对这些化合物的抗HCV活性是重要的。结论：抑制Hsc 70在宿主细胞中的表达以限制HCV的复制是一种潜在的抗HCV策略。菲啶类可能是具有这种作用模式的HCV抑制剂。
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.