Inhibition of Subgenomic Hepatitis C Virus RNA Replication by Acridone Derivatives: Identification of an NS3 Helicase Inhibitor

被引：50

作者：

Manfroni, Giuseppe ^{[1
]}

Paeshuyse, Jan ^{[2
]}

Massari, Serena ^{[1
]}

Zanoli, Samantha ^{[3
]}

Gatto, Barbara ^{[4
]}

Maga, Giovanni ^{[3
]}

Tabarrini, Oriana ^{[1
]}

Cecchetti, Violetta ^{[1
]}

Fravolini, Arnaldo ^{[1
]}

Neyts, Johan ^{[2
]}

机构：

[1] Univ Perugia, Dipartimento Chim & Tecnol Farm, I-06123 Perugia, Italy

[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

[3] CNR, Ist Genet Mol, I-27100 Pavia, Italy

[4] Univ Padua, Dipartimento Sci Farmaceut, I-35131 Padua, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 10期

关键词：

DNA TOPOISOMERASE-II; VIRAL DIARRHEA VIRUS; DEHYDROGENASE; RIBAVIRIN; MODEL; DISCOVERY; PROTEIN; AGENTS;

D O I：

10.1021/jm801608u

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis and structure - activity relationship (SAR) of a large series of acridones and acridone-fragment derivatives designed on the basis of the selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as a potential antibovine viral diarrhea virus (BVDV) compound. The evaluation of their ability to inhibit the HCV replication in Huh-5-2 cells led to the identification of new, selective inhibitors. This indicates that the acridone skeleton, when properly functionalized, is a suitable scaffold to obtain potential anti-HCV agents. Interestingly, during identification of possible cellular and viral targets, it was discovered that compound 23 exerts inhibitory activity on the HCV NS3 helicase, a very promising target for the development of anti-HCV drugs.

引用

页码：3354 / 3365

页数：12

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