Understanding the mechanism of action of the novel SSAO substrate (C7NH10)6(V10O28).2H2O, a prodrug of peroxovanadate insulin mimetics

Chem Biol Drug Des. 2007 Jun;69(6):423-8. doi: 10.1111/j.1747-0285.2007.00516.x.

Abstract

A new vanadium salt, hexakis(benzylammonium) decavanadate (V) dihydrate (C(7)NH(10))(6)(V(10)O(28)).2H(2)O (1), has been synthesized as well as characterized chemically and biologically. An in vitro enzyme assay revealed that compound 1 is oxidized to the same extent as a combination of benzylamine and vanadate by the enzyme semicarbazide-sensitive amine oxidase (SSAO), and therefore can be considered an SSAO substrate. It also stimulates glucose uptake in isolated rat adipocytes in a dose-dependent manner. We describe here the results of (51)V-NMR experiments that, combined with the in vitro results, corroborate that compound 1 could act as a prodrug of di-peroxovanadate ([V(OH)(2)(OO)(2)(OH)(2)](2-)) insulin mimetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Amine Oxidase (Copper-Containing) / chemistry
  • Animals
  • Benzylamines / chemistry*
  • Benzylamines / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Hypoglycemic Agents / pharmacology*
  • Insulin / chemistry*
  • Kinetics
  • Mice
  • Prodrugs / chemistry*
  • Rats
  • Rats, Wistar
  • Substrate Specificity
  • Vanadates / chemistry*
  • Vanadates / pharmacology*

Substances

  • Benzylamines
  • Hypoglycemic Agents
  • Insulin
  • Prodrugs
  • peroxovanadate
  • Vanadates
  • benzylamine
  • Amine Oxidase (Copper-Containing)