Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
Department of Molecular Biology, John Paul II Catholic University of Lublin, Poland.
Bioorg Med Chem Lett. 2014 Jan 15;24(2):609-12. doi: 10.1016/j.bmcl.2013.12.012. Epub 2013 Dec 9.
The bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50 μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor-enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein.
细菌天然产物 UK-1 和几种结构类似物在复制子测定中抑制丙型肝炎病毒的复制，其 IC50 值低至 0.50 μM。已鉴定出 NS3 解旋酶是这些化合物中几种可能的抑制靶标，而其余抑制剂则通过未知机制发挥作用。凝胶迁移分析表明，解旋酶抑制是抑制剂-酶结合的直接结果，而不是直接的 RNA 结合，并且 NS3 的 ATP 酶活性不受影响。本文介绍了它们的合成和生物学结果。
