Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase.
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.
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
Yang
Y
Li
Department of Pharmacology, Emory University , Atlanta, Georgia 30322, United States.
Thota
T
Ganesh
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
Becky A
BA
Diebold
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
Yerun
Y
Zhu
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
James W
JW
McCoy
Department of Molecular and Cellular Biology, Kennesaw State University , Kennesaw, Georgia 30144, United States.
Susan M E
SM
Smith
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
Aiming
A
Sun
Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.
J David
JD
Lambeth
Myeloperoxidase; NADPH-oxidase; inflammation; therapeutic; thioxo-dihydroquinazolin-one