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Author Notes:

Co-corresponding authors: AAK, JPB

Subjects:

Research Funding:

This research was partially funded by Union University.

The authors are grateful for the HRESMS data provided by D. R. Phillips and C.-W. Chou [Proteomics and Mass Spectrometry (PAMS) Facility, NIH grant 1S10RR1028859] at the University of Georgia, Department of Chemistry, Athens, Georgia.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physical Sciences
  • Biochemistry & Molecular Biology
  • Chemistry, Medicinal
  • Chemistry, Organic
  • Pharmacology & Pharmacy
  • Chemistry
  • NADPH oxidases
  • Nox4
  • Reactive oxygen species (ROS)
  • Pharmacophore development
  • Molecular modeling
  • OXIDATIVE STRESS
  • NAD(P)H OXIDASE
  • DIABETIC-NEPHROPATHY
  • THERAPEUTIC TARGETS
  • IN-VIVO
  • SUPEROXIDE
  • EXPRESSION
  • KIDNEY
  • HYPERTENSION
  • HYPERTROPHY

Design, synthesis, and biological evaluation of inhibitors of the NADPH oxidase, Nox4

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Journal Title:

Bioorganic and Medicinal Chemistry

Volume:

Volume 26, Number 5

Publisher:

, Pages 989-998

Type of Work:

Article | Post-print: After Peer Review

Abstract:

NADPH oxidases (Nox enzymes) are critical mediators of both physiologic and pathophysiologic processes. Nox enzymes catalyze NADPH-dependent generation of reactive oxygen species (ROS), including superoxide and hydrogen peroxide. Until recently, Nox4 was proposed to be involved exclusively in normal physiologic functions. Compelling evidence, however, suggests that Nox4 plays a critical role in fibrosis, as well as a host of pathologies and diseases. These considerations led to a search for novel, small molecule inhibitors of this important enzyme. Ultimately, a series of novel tertiary sulfonylureas (23–25) was designed using pharmacophore modeling, synthesized, and evaluated for inhibition of Nox4-dependent signaling.

Copyright information:

© 2017 Elsevier Ltd

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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