Nobuo Ikota

Efficient radical scavenging ability of artepillin C, a major component of Brazilian propolis, and the mechanism

Hydrogen transfer from artepillin C to cumylperoxyl radical proceeds via one-step hydrogen atom transfer rather than via electron transfer, the rate constant of which is comparable to that of (+)-catechin, indicating that artepillin C can act as an efficient antioxidant.

Chiral Pyrrolidine Derivatives as Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes

Abstract A series of pyrrolidine derivatives with β-amino alcohol moieties prepared from (S)-proline were found to catalyze the enantioselective addition of diethylzinc to aldehydes to yield optically active secondary alcohols with high enantioselectivities. A mechanism accounting for the configurational change with the bulkiness of chiral ligands is proposed.

Synthesis of (2R,3S)-2-hydroxymethyl-3-hydroxypyrrolidine and the Geissman-Waiss lactone from (S)-pyroglutamic acid

The synthesis of (2R,3S)- and (2R,3R)-2-hydroxymethyl-3-hydroxypyrrolidine derivatives and the Geisman-Waiss lactone has been achieved from (S)-pyroglutamic acid

Biting reduces acute stress-induced oxidative stress in the rat hypothalamus.

Abstract We investigated the inhibitory effect of para-masticatory activity, namely biting, on restraint stress-induced oxidative stress. A blood brain barrier-permeable nitroxyl spin probe, 3-methoxycarbonyl-2,2,5,5,-tetramethylpyrrolidine-1-oxyl (MC-PROXYL), was administered to rats and L-band electron spin resonance (ESR) and ESR-computerized tomography (ESR-CT) imaging were used to show that the decay rate constant of MC-PROXYL in the hypothalamus of isolated brain after 30 min of restraint stress was more rapid than in unrestrained control rats, suggesting that restraint was associated with oxidative stress. Interestingly, biting during restraint stress caused the decay rate constant of MC-PROXYL in isolated brain to approach that of the control group. These observations suggest that biting suppresses oxidative stress induced by restraint stress, and that the anti-stress effect of masticatory motor activity movements, such as biting, are important for reducing the adverse effects associated with exposure to psychological stressors.

Copper(II) complexes of l-histidylglycyl-l-histidylglycine and l-histidyl-l-histidylglycylglycine: Coordination mode of histidyl residues

Abstract The complex formations of L-histidylglycyl-L- histidylglycine (His-Gly-His-Gly) and L-histidyl-L- histidylglycylglycine (His-His-Gly-Gly) with copper- (II) ion were studied in a slightly alkaline medium by visible absorption, circular dichroism and electron spin resonance spectroscopies. His-Gly-His-Gly coordinates to copper(II) ion via a terminal amino nitrogen, two deprotonated peptide nitrogens and an imidazole nitrogen of the histidyl residue in the third position. The copper(II) ion in the His-His- Gly-Gly complex is coordinated by three nitrogen donors; i.e. , a terminal amino nitrogen, an adjacent deprotonated peptide nitrogen and an imidazole nitrogen of the histidyl residue in the second position. The imidazole nitrogen at the N-terminal does not participate in the chelate formation with the copper(II) ion, but it bridges between the two monomeric complexes so that a broad ESR spectrum without the hyperfine structure is observed.

Heterogeneity of Regional Redox Status and Relation of the Redox Status to Oxygenation in a Tumor Model, Evaluated Using Electron Paramagnetic Resonance Imaging

It is widely accepted that redox status, along with the partial pressure of oxygen (pO(2)), determines the efficacy of some therapeutic methods applied to treat tumors, including radiation. Redox status, evaluated by the reduction of a nitroxyl probe, was reportedly heterogeneous in a mouse tumor model. However, neither variation of heterogeneity of the redox status among mice nor the relation of the redox status to pO(2) in tumors has been characterized sufficiently. In this study, the regional reduction status in a mouse radiation-induced fibrosarcoma tumor model was evaluated using sequential three-dimensional electron paramagnetic resonance (EPR) imaging after i.v. injection of a tissue-permeable nitroxyl probe, HM-PROXYL. The regional decay of HM-PROXYL signal obeyed first-order kinetics, and the amplitude of the reduction rate and extent of its heterogeneity in a tumor varied among six mice. The tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine (LiPc) microcrystals implanted within the tumor. The location of LiPc was determined with EPR imaging. A sequential image was obtained following the injection of HM-PROXYL, even after LiPc implantation, by choosing an HM-PROXYL signal peak which does not overlap with the signal of LiPc. The relationship between pO(2) and the reduction rate at the region of pO(2) measurement was found to be low (r = 0.357) in 13 tumor-bearing mice, indicating that the extent of oxygenation does not necessarily affect the redox status under air-breathing conditions. The results strongly indicate the necessity of measurements of both redox status and oxygenation in every tumor to characterize tumor physiology.

Kinetic study of the electron-transfer oxidation of the phenolate anion of a vitamin E model by molecular oxygen generating superoxide anion in an aprotic medium.

Electron-transfer reduction of molecular oxygen (O2) by the phenolate anion (1-) of a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), occurred to produce superoxide anion, which could be directly detected by a low-temperature EPR measurement. The rate of electron transfer from 1- to O2 was relatively slow, since this process is energetically unfavourable. The one-electron oxidation potential of 1- determined by cyclic voltammetric measurements is sufficiently negative to reduce 2,2-bis(4-tert-octylphenyl)-1-picrylhydrazyl radical (DOPPH*) to the corresponding one-electron reduced anion, DOPPH-, suggesting that 1- can also act as an efficient radical scavenger.

STEREOSELECTIVE SYNTHESIS OF ALEXINE STEREOISOMERS FROM (S)-PYROGLUTAMIC ACID

Four stereoisomers of alexine (1,7a-diepialexine ( 1a ), 1,7,7a-triepialexine ( 1b ), 1-epialexine ( 30a ), and 1,7-diepialexine ( 30b )), the polyhydroxylated pyrrolizidine alkaloid, were synthesized from ( S )-pyroglutamic acid derivative ( 6 ).

Spin trapping for nitric oxide produced in LPS‐treated mouse using various new dithiocarbamate iron complexes having substituted proline and serine moiety

Four dithiocarbamate derivatives of 4‐substituted L‐proline and N‐methyl‐L‐serine were synthesized, and their iron complexes were prepared in Tris‐HCl buffer solution. These complexes were used as spin trapping reagents for nitric oxide in ESR spectrometry, and compared with each other in regard to their spin trapping properties in vivo. When the synthesized complexes were injected to lipopolysaccharide‐treated mice intravenously, the nitric oxide adducts were detected both in the liver and in the blood except N‐dithiocarboxy‐4‐(methoxymethyl)oxy‐L‐proline iron complex, whose nitric oxide adduct was detected mostly in the blood. When the exogenous nitric oxide adduct of this complex was injected, it was not detected in the liver, too. It is considered that this complex can trap nitric oxide in the blood by excluding the accumulation of the nitric oxide adduct in the liver.

In-vivo PET imaging of inducible D2R reporter transgene expression using [11C]FLB 457 as reporter probe in living rats

BackgroundIncreasing interest is being shown in a variety of methods for the in-vivo monitoring of gene expression. Of these, the reporter assay using positron emission tomography (PET) has been studied most extensively. MethodsWe evaluated tetracycline-induced gene expression using a PET reporter method employing the dopamine type 2 receptor (D2R) gene as a reporter gene and [11C]FLB 457 as a reporter probe. We constructed a plasmid containing the D2R gene, whose expression was under the control of the tetracycline-responsive element, and transfected it into HeLa-Tet-On cells. D2R messenger RNA (mRNA) expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) and D2R binding in the cultured cells was measured by a binding assay using methoxy-[3H]raclopride as a ligand. The tetracycline analogue, doxycycline, was used to regulate D2R expression. ResultsDoxycycline dose- and exposure time-dependent D2R transgene expression was observed in the mRNA measurements and receptor binding in the cells. The stably transfected cells were inoculated into nude rats and D2R expression in xenograft tumours was monitored by in-vivo receptor binding using PET. Doxycycline-dependent D2R expression was also observed in this in-vivo system. The correlation between the magnitude of the [11C]FLB 457 PET signal and the D2R-expressing cell fraction in the tumours showed the usefulness of the D2R–FLB 457 reporter gene–reporter probe system with PET for the quantitative evaluation of inducible in-vivo gene expression. ConclusionThe D2R–FLB 457 reporter gene–reporter probe system should be considered as a useful technique for measuring inducible in-vivo gene expression.