Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase

ACS Med Chem Lett. 2015 Aug 31;6(10):1047-52. doi: 10.1021/acsmedchemlett.5b00287. eCollection 2015 Oct 8.


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.

Keywords: Myeloperoxidase; NADPH-oxidase; inflammation; therapeutic; thioxo-dihydroquinazolin-one.