Parallel Synthesis, Evaluation, and Preliminary Structure-Activity Relationship of 2,5-Diamino-1,4-benzoquinones as a Novel Class of Bivalent Anti-Prion Compound

被引：32

作者：

Bongarzone, Salvatore ^{[2
,3
]}

Hoang Ngoc Ai Tran ^{[1
]}

Cavalli, Andrea ^{[4
,5
]}

Roberti, Marinella ^{[4
]}

Carloni, Paolo ^{[1
,2
,3
,6
]}

Legname, Giuseppe ^{[1
,4
]}

Bolognesi, Maria Laura ^{[4
]}

机构：

[1] SISSA, Lab Prion Biol, Neurobiol Sector, I-34151 Trieste, Italy

[2] SISSA, Stat & Biol Phys Sector, Neurobiol Sector, I-34136 Trieste, Italy

[3] Italian Inst Technol, SISSA ISAS Unit, I-34151 Trieste, Italy

[4] Univ Bologna, Dept Pharmaceut Sci, Alma Mater Studiorum, I-40126 Bologna, Italy

[5] Italian Inst Technol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy

[6] CNR, INFM, DEMOCRITOS Modeling Ctr Res Atomist Simulat, I-34151 Trieste, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 22期

关键词：

QUINOLINE DERIVATIVES; ANTIPRION; PROTEIN; ACRIDINE; THERAPEUTICS; INHIBITION; OXIDATION; ANALOGS; DESIGN;

D O I：

10.1021/jm100882t

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A library of 11 entries, featuring a 2,5-diamino-1,4-benzoquinones nucleus as spacer connecting two aromatic prion recognition motifs, was designed and evaluated against prion infection. Notably. 6-chloro-1,2,3,4-tetrithydroacridine 10 showed an EC50 of 0.17 mu M, which was lower than that displayed by reference compound BiCappa. More importantly, 10 possessed the capability to contrast prion fibril formation and oxidative stress, together with a low cytotoxicity. This study further corroborates the bivalent strategy as a viable approach to the rational design of anti-prion chemical probes.

引用

页码：8197 / 8201

页数：5

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