Search

We developed a physiologically based pharmacokinetic (PB-PK) model for spin-labeled drugs in animals and applied it for analyzing the decay curves of spin probes in the organs of mice as measured by multisite detection L-band ESR (MSD-LESR). The proposed method will be useful for not only understanding the PK features of nitroxyl radicals as spin probes but also developing spin-labeled drugs as a substitute for radio-isotope-labeled drugs.

Insulin-mimetic and anti-diabetic activities of bis(hinokitiolato)Zn(II) complex, Zn(hkt)2, with Zn(O4) coordination mode were evaluated. This complex was found to have the highest insulinomimetic ...

Vanadyl-meso-tetrakis(4-sulfonatophenyl)porphyrin, VOTPPS, was synthesized and evaluated for its in vitro and in vivo insulin-mimetic activities in streptozotocin (STZ)-induced diabetic mice. Based...

Zn(ll) complexes of allixin and its sulfur and N-methyl analogs were newly prepared, and their insulin-mimetic activities were evaluated. Among them, a new bis(1,6-dimethyl-3-hydroxy-5-methoxy-2-pentyl-1,4-dihydropyridine-4-thionato)-zinc(II) complex exhibited the most potent insulin-mimetic activity (IC 5 0 = 11 μM) in terms of inhibition of free fatty acid release in adipocytes.

Four kinds of vanadyl–hydroxythiazolethione complexes with VO(S2O2) coordination mode were newly synthesized, and demonstrated for the first time that the insulinomimetic activity apparently correl...

Binding feature of the vanadyl ion (VO2+) with bovine serum albumin (BSA) was studied with CD spectrometry based on comparisons with that of Cu2+. The strong positive CD band at 590 nm in the VO2+–albumin system was assigned to the binding of VO2+ and thiolate of Cys-34 in BSA.

Reaction of vanadyl sulfate with 3-hydroxypyridine-2-carboxylic acid (H2hpic) affords two chargeless complexes, [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)]·3H2O (1) and unprecedented cyclic tetranuclear complex [(VO)4(μ-(hpic-O,O′,N))(H2O)4]·8H2O (2), which were characterized by X-ray crystallographic analysis. The unique structural transformation between complexes 1 and 2 was found.

Three Zn(II) complexes with nicotinamide(na), nicotinemethylamide(nma), and nicotineethylamide(nea) were found to have in vitro insulinomimetic activities. X-ray structure analysis of [Zn(nea)2(H2O)2(SO4)]n showed that each nitrogen atom of two nea molecules locates trans, and the two water molecules and each oxygen atom of the two sulfates coordinate to a Zn(II) ion, forming an octahedral geometry of Zn(N2O4) unit in an inorganic polymer crystal. The Zn(II) complexes with na, nma, and nea exhibited higher insulinomimetic activities, respective IC50 values (50% inhibition concentration of the complex in the free fatty acids release from rat adipocytes) being 1.34, 1.12, and 0.96 mM, than that of ZnSO4 (IC50 = 1.52 mM).

Four kinds of vanadyl complexes of hydroxyazine-type heterocycles were synthesized. Bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)- and bis(1,2-dihydro-2-oxo-3,5,6-trimethyl-1-pyrazinolato)oxovanadium(IV) complexes showed higher insulin-mimetic activity than vanadyl sulfate as a positive control.

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.

A new purple vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), VO(OPT), with VO(S2O2) coordination mode, was prepared by mixing 2-mercaptopyridine-N-oxide or 1-hydroxy-2-pyridinethione and VOSO4, and characterized by UV, IR and EPR spectra, magnetic susceptibility and partition coefficient. Based on the higher in vitro insulin-mimetic activity of VO(OPT) (IC50 = 0.19 mM) than that of VOSO4 (IC50 = 0.9 mM), the complex was found to be a potent agent for treating insulin-dependent diabetes mellitus in rats when given by daily intravenous injection or oral administration.

A novel dinuclear Mn(II) complex, [Mn(L)(H2O)]2(ClO4)2 (1) where L is N,N-bis(2-pyridylmethyl)-(S)-histidinate, was synthesized. X-ray structure analysis of 1 revealed that each Mn(II) ion is a doubly carboxylate-bridged sevencoordinate structure. Cyclic voltammmetry indicated that electrode reaction of 1 was dependent on pH. The reactivity toward superoxide was evaluated by in vitro xanthine-xanthine oxidase-cytochrome c assay. The IC50 value of 1 is equal to 0.29 μM (1 M = 1 mol dm−3), which is one of the highest values in Mn(II) SOD mimetic complexes.

We prepared [VO(GeG)(H2O)] and [VO(MeM)(H2O)] by a reaction of VOSO4 with GeG and MeM. X-ray analyses of the complexes showed that a tetradentate ligand (GeG or MeM), an oxygen atom, and a water molecule were coordinated with the vanadium(IV) ion forming distorted octahedral geometries. In in vitro evaluation using isolated rat adipocytes, VO(GeG) (IC50=0.42 mM) was found to be more active at lower concentrations than VO(MeM)(IC50=17.0 mM) and VOSO4 (IC50=6.0 mM) in terms of IC50 values, 50% inhibition concentration of the FFA release from adipocytes.

An Egg-Yolk lecithin liposome containing the surfacant cyclic polyamine was prepared, and a dynamical behavior of its Cu(II) ion uptake was studied by monitoring a time dependent decay of the isotropic copper nucleus hyperfine splitting in the ESR upon metal incorporation into a liposomal membrane. The reaction kinetics studied by ESR justified the fact that there are the two kinds of metal binding processes, in which the distinctive time course and the activation energy can be clearly demonstrated.