4.4 Article

Understanding the mechanism of action of the novel SSAO substrate (C7NH10)(6)(V10O28)center dot 2H(2)O, a prodrug of peroxovanadate insulin mimetics

Journal

CHEMICAL BIOLOGY & DRUG DESIGN
Volume 69, Issue 6, Pages 423-428

Publisher

BLACKWELL PUBLISHING
DOI: 10.1111/j.1747-0285.2007.00516.x

Keywords

benzylamine vanaclate; diabetes; insulin mimetic; prodrug design

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A new vanadium salt, hexakis(benzylammonium) decavanadate (V) dihydrate (C7NH10)(6)(V10O28)(.)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 V-51-NMR experiments that, combined with the in vitro results, corroborate that compound 1 could act as a prodrug of di-peroxovanadate ([V(OH)(2)(00)(2)(OH)(2)](2-)) insulin mimetics.

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