Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole as a novel anti-hepatitis C virus targeting scaffold.
Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole as a novel anti-hepatitis C virus targeting scaffold.
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DOI：
10.1016/j.ejmech.2015.04.022
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发表时间：
2015
影响因子：
6.7
通讯作者：
Kurkin AV
中科院分区：
文献类型：
--
作者：
Andreev IA;Manvar D;Barreca ML;Belov DS;Basu A;Sweeney NL;Ratmanova NK;Lukyanenko ER;Manfroni G;Cecchetti V;Frick DN;Altieri A;Kaushik-Basu N;Kurkin AV
尽管全口服直接作用抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）现已成为现实，但如今的HCV药物价格昂贵，仍迫切需要更实惠的药物。在这项工作中，我们报告了抑制HCV基因型1b和2a亚基因组复制子细胞复制的2-苯基-4，5，6，7-四氢-1H-吲哚化学支架的鉴定。本文描述了抗-HCV基因型1b和2a谱和对所选代表性衍生物组的细胞活力的影响以及它们的化学合成。最有效的化合物39在基因型1b和2a中的EC 50值分别为7.9和2.6 μM。生化分析表明，衍生物39对HCV NS 5 B聚合酶、NS 3解旋酶、IRES介导的翻译和选择的宿主因子无影响。因此，未来的工作将涉及2-苯基-4，5，6，7-四氢-1H-吲哚作为新的抗HCV药物的化学优化和靶标鉴定。
Although all-oral direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) treatment is now a reality, today's HCV drugs are expensive, and more affordable drugs are still urgently needed. In this work, we report the identification of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole chemical scaffold that inhibits cellular replication of HCV genotype 1b and 2a subgenomic replicons. The anti-HCV genotype 1b and 2a profiling and effects on cell viability of a selected representative set of derivatives as well as their chemical synthesis are described herein. The most potent compound 39 displayed EC50 values of 7.9 and 2.6 µM in genotype 1b and 2a, respectively. Biochemical assays showed that derivative 39 had no effect on HCV NS5B polymerase, NS3 helicase, IRES mediated translation and selected host factors. Thus, future work will involve both the chemical optimization and target identification of 2-phenyl-4,5,6,7-Tetrahydro-1H-indoles as new anti-HCV agents.
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影响因子：
6.7
作者：
Manvar, Dinesh;Pelliccia, Sveva;Silvestri, Romano
通讯作者：
Silvestri, Romano
影响因子：
3.7
作者：
Lin YT;Wu YH;Tseng CK;Lin CK;Chen WC;Hsu YC;Lee JC
通讯作者：
Lee JC
影响因子：
7.3
作者：
Manfroni G;Manvar D;Barreca ML;Kaushik-Basu N;Leyssen P;Paeshuyse J;Cannalire R;Iraci N;Basu A;Chudaev M;Zamperini C;Dreassi E;Sabatini S;Tabarrini O;Neyts J;Cecchetti V
通讯作者：
Cecchetti V
影响因子：
7.6
作者：
Lee, Jin-Ching;Chen, Wei-Chun;Wu, Yang-Chang
通讯作者：
Wu, Yang-Chang
影响因子：
7.3
作者：
Li, Kelin;Frankowski, Kevin J.;Belon, Craig A.;Neuenswander, Ben;Ndjomou, Jean;Hanson, Alicia M.;Shanahan, Matthew A.;Schoenen, Frank J.;Blagg, Brian S. J.;Aube, Jeffrey;Frick, David N.
通讯作者：
Frick, David N.