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Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase

Yang Li1, Thota Ganesh2, Becky A Diebold1

  • 1Department of Pathology and Laboratory Medicine, Emory University , Atlanta, Georgia 30322, United States.

ACS Medicinal Chemistry Letters
|October 22, 2015
PubMed

Insights

Researchers developed novel quinazolin-4(1H)-one compounds that effectively inhibit myeloperoxidase (MPO), an enzyme implicated in inflammatory and neurodegenerative diseases like Parkinson's and Alzheimer's.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Neuroscience

Background:

  • Myeloperoxidase (MPO) is an enzyme crucial for host defense but also implicated in inflammatory processes.
  • MPO activity is linked to the pathogenesis of neuroinflammatory diseases, including Parkinson's and Alzheimer's disease.

Purpose of the Study:

  • To synthesize and characterize novel quinazolin-4(1H)-one derivatives as potential inhibitors of MPO.
  • To evaluate the inhibitory potential of these compounds against MPO for therapeutic applications.

Main Methods:

  • Synthesis and characterization of over 50 quinazolin-4(1H)-one derivatives.
  • Enzyme inhibition assays to determine IC50 values and mechanism of inhibition (e.g., substrate competition).

Main Results:

  • Over 50 quinazolin-4(1H)-one derivatives were synthesized and characterized.
  • Compounds demonstrated potent MPO inhibition with IC50 values down to 100 nM.
  • Inhibition was partially reversible and competitive with respect to Amplex Red, without Compound II accumulation.

Conclusions:

  • Quinazolin-4(1H)-one derivatives represent a promising class of MPO inhibitors.
  • These compounds hold potential for therapeutic development in diseases driven by MPO-mediated inflammation.
Keywords:
MyeloperoxidaseNADPH-oxidaseinflammationtherapeuticthioxo-dihydroquinazolin-one

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