Applied Molecular Virology, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
Medicinal Chemistry Group, Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, Republic of Korea.
Eur J Med Chem. 2014 May 6;78:35-42. doi: 10.1016/j.ejmech.2014.03.030. Epub 2014 Mar 13.
In this report we describe 2-iminobenzimidazole (IBI) analogs, identified during the course of a phenotypic high-throughput screening campaign, as novel hepatitis C virus (HCV) inhibitors. A series of IBI derivatives was synthesized and evaluated for their inhibitory activity against infectious HCV. Among the IBIs derivatives studied in this work, we identified promising compounds with high antiviral efficacy, high selectivity index and good microsomal stability. Noteworthy, the IBI series exhibited inhibitory activity on early and late steps of the viral cycle, but not in the HCV replicon system demonstrating a mechanism of action distinct from clinical-stage and approved anti-HCV drugs. Overall, our results suggest that IBIs are predestinated for further exploration as lead compounds for novel HCV interventions.
在本报告中，我们描述了在表型高通量筛选过程中发现的 2-亚氨基苯并咪唑（IBI）类似物，它们是新型丙型肝炎病毒（HCV）抑制剂。合成了一系列 IBI 衍生物，并评估了它们对感染性 HCV 的抑制活性。在本工作研究的 IBIs 衍生物中，我们确定了具有高抗病毒功效、高选择性指数和良好的微粒体稳定性的有前途的化合物。值得注意的是，该 IBI 系列在病毒周期的早期和晚期步骤均具有抑制活性，但在 HCV 复制子系统中没有抑制活性，表明其作用机制与临床阶段和批准的抗 HCV 药物不同。总体而言，我们的结果表明，IBI 适合进一步探索作为新型 HCV 干预措施的先导化合物。
