Aryl azoles with neuroprotective activity - Parallel synthesis and attempts at target identification

被引：40

作者：

Cocconcelli, Giuseppe ^{[1
]}

Diodato, Enrica ^{[1
]}

Caricasole, Andrea ^{[1
]}

Gaviraghi, Giovanni ^{[1
]}

Genesio, Eva ^{[1
]}

Ghiron, Chiara ^{[1
]}

Magnoni, Letizia ^{[1
]}

Pecchioli, Elena ^{[1
]}

Plazzi, Pier Vincenzo ^{[2
]}

Terstappen, Georg C. ^{[1
]}

机构：

[1] Siena Biotech SpA, I-53100 Siena, Italy

[2] Univ Parma, Dipartimento Farmaceutico, I-43100 Parma, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 04期

关键词：

D O I：

10.1016/j.bmc.2007.10.090

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A parallel synthesis of aryl azoles with neuroprotective activity is described. All compounds obtained were evaluated in an in vitro assay using a NMDA toxicity paradigm showing a neuroprotective activity between 15% and 40%. The potential biological target of the active compounds was investigated by extensive literature searches based around similar scaffolds with reported neuroprotective activity. The most interesting molecules active in the NMDA toxicity assay (3a and 2g) showed moderate but significant activity in the inhibition of the Site 2 Sodium Channel binding assay at 10 mu M. To confirm our hypothesis compounds 3a, c, f and 2g were tested in the Veratridine assay which is one of the excitotoxicity assays of revelance to NaV channels. The compounds tested showed an activity between 40% and 70%. The identification of neuroprotective small molecules and the identification of NaV channels as the potential site of action were the most important goals of this work. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2043 / 2052

页数：10

共 48 条

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