Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase

详细信息    查看全文

• 作者：Yang Li ; Thota Ganesh ; Becky A. Diebold ; Yerun Zhu ; James W. McCoy ; Susan M. E. Smith ; Aiming Sun ; J. David Lambeth
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：October 8, 2015
• 年：2015
• 卷：6
• 期：10
• 页码：1047-1052
• 全文大小：381K
• ISSN：1948-5875

文摘

Myeloperoxidase (MPO) is a key antimicrobial enzyme, playing a normal role in host defense, but also contributing to inflammatory conditions including neuroinflammatory diseases such as Parkinson鈥檚 and Alzheimer鈥檚. We synthesized and characterized more than 50 quinazolin-4(1H)-one derivatives and showed that this class of compounds inhibits MPO with IC₅₀ values as low as 100 nM. Representative compounds showed partially reversible inhibition that was competitive with respect to Amplex Red substrate and did not result in the accumulation of MPO Compound II. Members of this group show promise for therapeutic development for the treatment of diseases in which inflammation plays a pathogenic role.