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Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase.

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.

SUBMITTER: Li Y

PROVIDER: S-EPMC4601060 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase.

Li Yang Y Ganesh Thota T Diebold Becky A BA Zhu Yerun Y McCoy James W JW Smith Susan M E SM Sun Aiming A Lambeth J David JD

ACS medicinal chemistry letters 20150831 10

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 substr ...[more]

PMID: 26487910

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