Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase
Department
Molecular and Cellular Biology
Document Type
Article
Publication Date
8-31-2015
Abstract
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’s and Alzheimer’s. 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.
Journal Title
ACS Medicinal Chemistry Letters
Journal ISSN
1948-5875
Volume
6
Issue
10
First Page
1047
Last Page
1052
Digital Object Identifier (DOI)
10.1021/acsmedchemlett.5b00287