N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors

Bioorg Med Chem Lett. 2001 Sep 3;11(17):2377-80. doi: 10.1016/s0960-894x(01)00456-5.

Abstract

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arginine / metabolism
  • Dioxanes / chemistry*
  • Dioxanes / pharmacology*
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Guanidine / chemistry*
  • Guanidines / chemistry*
  • Guanidines / pharmacology*
  • Guinea Pigs
  • Horseradish Peroxidase / metabolism
  • Hydrogen Peroxide / chemistry
  • Hydrogen Peroxide / metabolism
  • In Vitro Techniques
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Nitric Oxide Donors / chemistry*
  • Nitric Oxide Donors / metabolism
  • Nitric Oxide Donors / pharmacology*
  • Nitric Oxide Synthase / metabolism*
  • Nitrites / metabolism
  • Structure-Activity Relationship
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / metabolism
  • Vasodilator Agents / pharmacology

Substances

  • Dioxanes
  • Guanidines
  • N-hydroxyguanoxan
  • Nitric Oxide Donors
  • Nitrites
  • Vasodilator Agents
  • Arginine
  • Hydrogen Peroxide
  • Horseradish Peroxidase
  • Nitric Oxide Synthase
  • Guanidine