Characterization and insulin-mimetic potential of oxidovanadium(IV) complexes derived from monoesters and -carboxylates of 2,5-dipicolinic acid

Abstract

The monomethyl ester 2MeOdipicH (1) of 2,5-dipicolinic acid, characterized as its magnesium salt [Mg(H2O)6]-(2MeOdipic)2, was converted, via the diesters 2MeO-5ROdipic and the copper complexes [Cu(5ROdipic)2], to the ligands 5ROdipicH (R = iPr 2a, (S)-2-Bu 2b). The proligands 2MeO-5ROdipic (with R = diisopropyl-D-galactose 2c, myo-inositol-orthoformate 2d) and 2MeO-5R′NHdipic (where R′ represents the ethyl-protected L-amino acid residues Gly 3a, Ala 3b, Val 3c and Phe 3d) were obtained from 2-MeO-5Cldipic and the amino acid ethyl esters. Reaction of 2 and 3 with VOSO4 afforded the complexes [VO(H 2O)(5ROdipic)2] (4a-d) and [VO(H2O) (5R′NHdipic)2], 5a-d, respectively. [Mg(H2O) 6](2MeOdipic)2·4H2O, 2b, 3a and 4a·0.5H2O were characterized by single-crystal X-ray diffraction analysis. Selected type 4 and 5 complexes were submitted to in vitro tests (fibroblasts, SV 3T3 mice fibroblasts) for their uptake kinetics and insulin-mimetic behavior. The compounds were comparable to insulin in their ability to stimulate cellular glucose uptake and metabolism. In vitro tests with rat adipocytes showed that the complexes also mimic the ability of insulin to inhibit lipolysis. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.