A family of insulinomimetic zinc(II) complexes of amino ligands with Zn(Nn) (n=3 and 4) coordination modes.

Several metal ions and their complexes have been known to mimic the action of insulin in in vitro and in vivo systems. We prepared a family of Zn(II) complexes derived from amino ligands with Zn(Nn) (n=3 and 4) coordination modes, the insulinomimetic activity being estimated by an inhibitory effect of free fatty acid release from isolated rat adipocytes treated with epinephrine. In comparison with the positive controls VOSO(4) and ZnSO(4), Zn(II)-amine complexes with stability constants (log beta) lower than 11.

In vitro alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide.

We found alpha-glucosidase inhibitory effect of Zn(II) complex with 6-methyl-2-picolinmethylamide (6mpa-ma) which showed the highest blood glucose lowering effect in Zn(II) complexes with picolinamide derivatives in KK-A(y) mice. The Zn(II) complex showed strong alpha-glucosidase inhibitory activity greater by about eighty times (substrate: maltose) and forty times (substrate: sucrose) compared with acarbose.

Metallokinetic study of zinc in the blood of normal rats given insulinomimetic zinc(II) complexes and improvement of diabetes mellitus in type 2 diabetic GK rats by their oral administration.

In order to understand the insulinomimetic activity of zinc(II) complexes, we studied the metallokinetic features of zinc in the blood of normal rats given the zinc complexes, bis(maltolato)zinc(II) (Zn(mal)(2)) and bis(6-methylpicolinato)zinc(II) (Zn(6mpa)(2)) by comparing each of them with an ionic form of zinc chloride (ZnCl(2)). The bioavailability of the zinc(II) complexes following oral administration was enhanced to 1.4-1.

A new insulin-mimetic bis(allixinato)zinc(II) complex: structure-activity relationship of zinc(II) complexes.

During the investigation of the development of insulin-mimetic zinc(II) complexes with a blood glucose-lowering effect in experimental diabetic animals, we found a potent bis(maltolato)zinc(II) complex, Zn(ma)(2), exhibiting significant insulin-mimetic effects in a type 2 diabetic animal model. By using this Zn(ma)(2) as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(ma)(2) and its related complexes. The in vitro insulin-mimetic activity of these complexes was determined by the inhibition of free fatty acid release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine.

The action mechanism of zinc(II) complexes with insulinomimetic activity in rat adipocytes.

Zinc (Zn), an essential trace element, and its complexes have recently been known to exhibit insulinomimetic activities. However, the action mechanism of Zn(II) has yet been obscure. The purpose of the present study was to estimate the action mechanism of the Zn(II) complexes.

Blood glucose lowering and toxicological effects of zinc (II) complexes with maltol, threonine, and picolinic acid.

The blood glucose lowering effects in KK-Ay mice with type 2 diabetes mellitus (DM) receiving daily an intraperitoneal (i.p.) administration of Zn(II) complexes with maltol, L-threonine, and picolinic acid for 14 days were estimated under the same conditions, and dose-dependent blood glucose lowering effects in the dose range of 0.

Synthesis, structure analysis, solution chemistry, and in vitro insulinomimetic activity of novel oxovanadium(IV) complexes with tripodal ligands containing an imidazole group derived from amino acids.

Structures, chemical properties, and in vitro insulinomimetic activities of new vanadyl [oxovanadium(IV), VO(2+)] complexes with five tripodal ligands containing an imidazole functionality were examined. The ligands, N-(carboxymethyl)- N-(4-imidazolylmethyl)amino acids, contain glycine, ( S)- and ( R)-alanine, and ( S)- and ( R)-leucine residues. The molecular structures of the latter four alanine- and leucine-containing complexes were determined by X-ray analysis.

Insulinomimetic zinc(II) complexes with natural products: in vitro evaluation and blood glucose lowering effect in KK-Ay mice with type 2 diabetes mellitus.

In vitro insulinomimetic activities of Zn(II) complexes with three natural products, betaine, L-lactic acid, and D-(-)-quinic acid (qui), were found in rat adipocytes treated with epinephrine in terms of the inhibition of free fatty acid release. Based on the results, the blood glucose lowering effect in KK-A(y) mice with type 2 diabetes mellitus was observed by daily i.p.

Anti-diabetes effect of Zn(II)/carnitine complex by oral administration.

A novel bis(L-carnitinato)Zn(II) complex, Zn(car)(2)Cl(2), was prepared, and its insulinomimetic and antidiabetic activities were examined. The complex showed a tendency to lower the high blood glucose levels of KK-A(y) mice with type 2 diabetes mellitus when given by oral administration at a dose of 20 mg Zn/kg body weight for 16 d. In addition, the complex improved glucose tolerance ability when examined by the oral glucose tolerance test (1 g glucose/kg body weight).

Potential insulinominetic agents of zinc(II) complexes with picolinamide derivatives: preparations of complexes, in vitro and in vivo studies.

Following the finding of in vitro insulinominetic activities of new prepared Zn(II) complexes with amide ligands (2-picolinamide (pa-a) and 6-methyl-2-picolinmethylamide (6mpa-ma)) in isolated rat adipocytes treated with epinephrine in terms of inhibition of free fatty acid release, their blood glucose normalizing effects were observed on daily intraperitoneal injections for 14 d in a type 2 diabetes mellitus model animal, KK-Ay mice. The blood glucose levels of KK-Ay mice were maintained in a normal range during the administration of both complexes. After the administration of each complex for 14 d, the improvement of glucose metabolism was confirmed as judged by the glucose tolerance test.

Development of new insulinomimetic zinc(II) picolinate complexes with a Zn(N2O2) coordination mode: structure characterization, in vitro, and in vivo studies.

Three zinc(II) complexes of picolinic acid and its derivatives with a Zn(N2O2) coordination mode were prepared and evaluated for their insulinomimetic activities by in vitro and in vivo studies. By introducing an electron-donating methyl group into the picolinate ligand (pic), bis(6- or 3-methylpicolinato)zinc(II) complexes [Zn(6-mpa)2 or Zn(3-mpa)2, respectively] were prepared. The Zn(6-mpa)(2) complex was crystallized as a water adduct [Zn(6-mpa)2(H2O)].

Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-A(y) mice.

A novel bis(6-ethylpicolinato)(H(2)O)oxovanadium(IV) complex (VO(6epa)(2) x (H(2)O)) was prepared and its structure was revealed by X-ray analysis (space group Pc(#7), a=10.838(2), b=11.148(5), c=16.