Novel symmetrical phenylenediamines as potential anti-hepatitis C virus agents

Q2 Pharmacology, Toxicology and Pharmaceutics Antiviral Chemistry and Chemotherapy Pub Date : 2015-12-01 DOI:10.1177/2040206616676353

Marcella Bassetto, S. Ferla, P. Leyssen, J. Neyts, Mark M Yerukhimovich, D. Frick, Rachel O'Donnell, A. Brancale

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引用次数: 2

Abstract

Background Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection. Methods With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay. Results Among the newly designed compounds, one new structural family was found to inhibit the hepatitis C virus-1b replication in the micromolar range. This scaffold was chosen for further exploration and different novel analogues were synthesised and evaluated. Conclusions Different new inhibitors of the hepatitis C virus genotype 1b replication were identified. Some of the new compounds show mild inhibition of the NS3 helicase enzyme.

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新型对称苯二胺作为潜在的抗丙型肝炎病毒药物

背景尽管在过去十年中取得了很大进展，但替代策略可能有助于改善针对丙型肝炎病毒感染的明确治疗方案。方法以寻找新的靶向病毒NS3解旋酶的丙型肝炎病毒-1b复制抑制剂为目的，对已有报道的对称型NS3解旋酶抑制剂的结构进行合理修饰，并根据对接研究筛选出4种新型支架进行合成，并在丙型肝炎病毒-1b亚基因组复制子实验中进行评价。结果在新设计的化合物中，发现一个新的结构家族在微摩尔范围内抑制丙型肝炎病毒-1b的复制。选择这种支架进行进一步的探索，并合成和评估了不同的新型类似物。结论发现了多种抑制丙型肝炎病毒基因型1b复制的新抑制剂。部分新化合物表现出对NS3解旋酶的轻度抑制作用。

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来源期刊

Antiviral Chemistry and Chemotherapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： Antiviral Chemistry & Chemotherapy publishes the results of original research concerned with the biochemistry, mode of action, chemistry, pharmacology and virology of antiviral compounds. Manuscripts dealing with molecular biology, animal models and vaccines are welcome. The journal also publishes reviews, pointers, short communications and correspondence.