Vanadium has well-documented lowering glucose properties both in vitro and in vivo. The design of new oxovanadium(IV) coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biological testing with oxovanadium(IV) organic phosphonic acid, for insulin-enhancing potential included acute administration, by oral gavage in streptozotocin (STZ) diabetic rats. The complexes of oxovanadium(IV) amino acid-N-phosphonic acid exhibit higher lowering glucose activity in vivo. The interaction of the complexes of oxovanadium(IV) amino acid-N-phosphonic acid with DNA was investigated by agarose gel electrophoresis. The results indicated that these complexes have strong interaction with DNA.Keywords oxovanadium, amino acid-N-phosphonic acid, lowering glucose activity, interaction
IntroductionDiabetes mellitus is a heterogeneous disorder. It is characterized by hyperglycemia, alterations in carbohydrate and lipid metabolism, and vascular and neurological complications. An underlying insufficiency of insulin results from either inadequate pancreatic production, 1,2 or defective insulin utilization. 3 Good diabetic control with available therapies continues to be an elusive goal. Thus, there is a need to find effective, orally active drugs that mimic or enhance the properties of insulin.Vanadium, a trace element in the environment, is found in plants and animals, and is also found as a vanadium enzyme, vanadium bromoperoxidase, in marine macroalgae, and thus the role of vanadium in biological functions has been extensively investigated. 4,5 The finding in 1980 that vanadate(V) has an insulin-mimetic effect, and studies indicating that vanadium directly affects glucose metabolism, have stimulated research on insulin-mimetic vanadium compounds. [6][7][8][9][10][11][12][13] Oral administration of insulin in mammals is ineffective; therefore, diabetic patients receive insulin by subcutaneous injection. The availability of orally administered insulin substitutes could be of importance in the treatment of diabetics.
Experimental
Chemicals and instrumentationAll solvents and chemicals were of reagent grade and used without further purification unless otherwise specified: glycine-N-methene phosphonic acid, alanine-N-methenephosphonic acid, vanadyl sulfate trihydrate. Water was deionized. The yields are for analytically pure compounds and calculations are based on vanadium. All complexation reactions were carried out under nitrogen.The complexes were characterized by IR spectra, elemental analyses, 31 P MAS NMR and 51 V NMR susceptibility. Elemental analyses were performed on a Perkin Elmer 2400 CHN Elemental analyzer. P and V were determined by PLASMA-SPEC (I) inductively coupled plasma spectrometer. Infrared spectra were recorded as KBr disks in the range 4000-400 cm -1 on a Magna FT-IR 560 spectrometer.51 V NMR spectra were obtained on a Varian Unity-...