Understanding the mechanism of action of the novel SSAO substrate (C7NH10)6(V10O28).2H2O, a prodrug of peroxovanadate insulin mimetics.
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.
Yraola
Francesc
F
Combinatorial Chemistry Unit, Barcelona Science Park, Josep Samitier 1, E-08028 Barcelona, Spain.
García-Vicente
Silvia
S
Marti
Luc
L
Albericio
Fernando
F
Zorzano
Antonio
A
Royo
Miriam
M
D017667:Adipocytes / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry; D000818:Animals; D001596:Benzylamines / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D011355:Prodrugs / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D014638:Vanadates / Q000737:chemistry* / Q000494:pharmacology*
D001596:Benzylamines; D007004:Hypoglycemic Agents; D007328:Insulin; D011355:Prodrugs; C069276:peroxovanadate; D014638:Vanadates; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing)