New Insulin-Mimetic Zinc (II) Complexes; Bis-maltolato Zinc(II) and Bis-(2-hydroxypyridine-N-oxido) Zinc(II) with Zn(O4) Coordination Mode

Abstract

Zinc(II) complexes with a Zn(O4) coordination mode were found to have insulinomimetic activity. A bis-maltolato zinc(II) (Zn(Mal)2) complex was revealed to be in an octahedral and a square pyramidal geometries in a unit cell. Both Zn(Mal)2 (IC50 = 0.59 mM) and bis-2-hydroxypyridine-N-oxide zinc(II) (IC50 = 0.41 mM) complexes exhibited higher insulinomimetic activity than VOSO4(IC50 = 1.00 mM) and ZnSO4(IC50 = 0.81 mM) in terms of IC50 values, which show 50% inhibition concentration of the complex in the free fatty acids release from rat adipocytes.

Anti-diabetes Effect of Zn(II)/Carnitine Complex by Oral Administration.

“…In conclusion, Zn(car) 2 Cl 2 has been found to have the in vitro insuinomimetic activity and in vivo blood glucose lowering effect, the improvement of the diabetes being supported by the results of the glucose tolerance test. The present result is the first example for the orally active Zn(II) complex.…”

“…Zn(car) 2 Cl 2 was found to be more active than VOSO 4 (IC 50 ϭ1.00Ϯ0.08 mM) and to have almost the same activity to that of ZnSO 4 (IC 50 ϭ0.81Ϯ0.10 mM). In our previous research, if IC 50 value of the VO compounds were equal to or less than 1.00 mM, the compounds showed antidiabetic activity by oral administration.…”

“…1) We reported that Zn(II) complexes with nicotinamide, maltol, amino acids, picolinic acid, picolinamide, and their derivatives have high insulinomimetic activities in in vitro and in vivo studies. [2][3][4][5][6][7] However, these complexes were effective in showing the lowering effect of blood glucose by daily intraperitonial injections to type 2 diabetes mellitus. When aiming at the clinical use of the complexes, it is essentially important to find complexes that are effective on oral administration.…”

“…15) On the other hand, the body uses L-carnitine to produce the enzyme, acetyl-L-carnitine transferase, which boosts choline metabolism and releases acetylcholine in the brain. 16,17) We synthesized the complex, Zn(car) 2 2 Cl 2 ). Therefore, we estimated the structure of Zn(car) 2 Cl 2 as shown in Fig.…”

A New Synthetic Method of Zinc(II) Complexes Based on Mixing

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] However, that method has the disadvantages of increased costs of Zn(II) complexes due to the alkali and large quantity of organic solvents required, along with the undesirable eŠects on the environment and human health alkali used. This paper reports a new method to obtain Zn(II) complexes at high yields (more than 90％) by direct mixing of solid ligands and solid Zn(OH) 2 or ZnO with or without the addition of a minimum amount of water without the use of alkali and organic solvents.…”