Title

Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase

Department

Molecular & 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

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