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| 1.
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論文
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Aoki, Katsuyuki ; Koseki, Jun-ichi ; Takeda, Shuichi ; Aburada, Masaki ; Miyamoto, Kenichi
概要:
金沢大学医学部附属病院薬剤部<br />It has already been reported that 3-(indol-2-yl)quinoxalin-2-ones 1)? have a potent inhibitory effec
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t on the growth of tumor cells based on anti-angiogenesis activity. We have also carried out a structure-activity relationship (SAR) study of 3-(indol-2-yl)quinoxalin-2-ones, which showed a potent inhibitory activity toward the vascular endothelial growth factor (VEGF)-induced proliferation of human mesangial cells and the VEGF-induced auto-phosphorylation of human umbilical vein endothelial cells.2) Moreover, one of these compounds has a potent medicinal effect based on anti-angiogenic action, by oral administration2) (Chart 1, 9). However, since the existing synthetic methods1) for the preparation of 3-(indol-2-yl)quinoxalin-2-ones consist of multiple steps some of which require strict anhydrous conditions, a convenient and simple synthetic method in place of the existing method is desirable. As a result of the investigations into the synthetic procedures, 3-(3-substituted indol-2-yl)quinoxalin-2-ones can be easily prepared by the condensation of 3-substituted indoles with quinoxalin-2-ones in the presence of trifluoroacetic acid (TFA). Herein, we report the examination of these reaction conditions and the application of this new synthetic method to the synthesis of the derivatives as VEGF inhibitors. © 2007 Pharmaceutical Society of Japan.
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Tao Le .
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Kudo, Tomoya ; Takino, Takahisa ; Miyamori, Hisashi ; Thompson, Erik W. ; Sato, Hiroshi
概要:
金沢大学がん研究所がん病態制御<br />Although tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to be not only an inhibitor of m
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atrix metalloproteinases (MMP) but also a cofactor for membrane-type 1 MMP (MT1-MMP)-mediated MMP-2 activation, it is still unclear how TIMP-2 regulates MMP-2 activation and cleavage of substrates by MT1-MMP. In the present study we examined the levels of cell-surface MT1-MMP, MMP-2 activation and cleavage of MT1-MMP substrates in 293T cells transfected with the MT1-MMP and TIMP-2 genes. Co-expression of TIMP-2 at an appropriate level increased the level of cell-surface MT1-MMP, both the TIMP-2-bound and free forms, and generated processed MMP-2 with gelatin-degrading activity. In contrast, MT1-MMP substrates testican-1 and syndecan-1 were cleaved by the cells expressing MT1-MMP, which was inhibited by TIMP-2 even at levels that stimulate MMP-2 activation. These results suggest that TIMP-2 environment determines MT1-MMP substrate choice between direct cleavage of its own substrates and MMP-2 activation. © 2007 Japanese Cancer Association.
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| 5.
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Alam, Shamiul ; Ueki, Koichiro ; Marukawa, Kohei ; Ohara, Teruhisa ; Hase, Takashi ; Takazakura, Daisuke ; Nakagawa, Kiyomasa
概要:
金沢大学医学部附属病院歯科口腔外科<br />Objectives: The purpose of this study was to histologically and immunohistochemically evaluate bo
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ne regeneration using 3 different implant materials in rabbit mandibles and to compare the bone regenerative capability of these materials in an animal model. Study design: Adult male Japanese white rabbits (n = 48; 12-16 wks old; 2.5-3.0 kg) were divided into 4 groups, consisting of 12 animals each. The implant materials were β-tricalcium phosphate (β-TCP), autologous bone derived from the radius, and recombinant human bone morphogenetic protein 2 (rhBMP-2) with polylactic acid/polyglycolic acid copolymer and gelatin sponge (PGS) complex. After incising along the inferior border of the mandible, the materials were implanted as only grafts and covered by titanium mesh with screws. No material was implanted into the control group. The rabbits were killed at 2, 4, 8, 12, and 24 wks postoperatively, and formalin-fixed specimens containing titanium mesh were embedded in acrylic resin. The specimens were stained with hematoxylin and eosin. For immunohistochemical analysis, the specimens were treated with BMP-2 and fibroblast growth factor 2 (FGF-2) antibodies. Finally, they were examined microscopically. Results: The autologous bone induced substantially more new bone formation compared with β-TCP at 4 wks postoperatively. However, rhBMP-2/PGS induced new bone formation at 8 wks postoperatively. No growth of bony tissue was observed in the control group at any period. In the autologous bone and rhBMP-2/PGS groups, both BMP-2 and FGF-2 were observed later in the β-TCP group than in other groups. Conclusion: This study suggests that autologous bone as well as rhBMP-2/PGS implants induce expression of both BMP-2 and FGF-2 specifically at the operated sites, even at early stages. © 2007 Mosby, Inc. All rights reserved.
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| 6.
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Ogawa, Toshikazu ; Kitoh, Sohichi ; Ogawa, Masaaki ; Ichitani, Masaki ; Kuwae, Akio ; Hanai, Kazuhiko ; Kunimoto, Koki
概要:
The crystal structure of the 1:2 dimethylsulfoxide solvate of 4,4′-diphenyl-2,2′-dithioxo-[4,4′-biimidazolidine]-5,5′-di
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one(I) has been determined by X-ray diffraction. The crystal belongs to space group C2/c with cell dimensions of a = 23.81(1)Å, b = 9.884(5)Å, c = 12.536(8)Å, β = 117.38(1)°. The compound, C18H14N4O2S2·2C2H6OS, crystallizes with half a molecule in the asymmetric unit, the molecule being centrosymmetric. The centre of inversion lies on the middle of the C(3)-C(3)′ bond. In crystals, the molecules form two N-H…O cyclic hydrogen bonds in a cyclic R22(12) arrangement, each of which forms on either side. DMSO molecules are hydrogen-bonded to the amide N-H groups. This hydrogen bond network forms an infinite tape structure along the c-axis.
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| 7.
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論文
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小谷, 明
概要:
金沢大学医薬保健研究域 薬学系<br />Ternary Cu(ii) complexes containing an aromatic diimine (DA = di(2-pyridylmethyl)amine (dpa), 4,4′-
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disubstituted 2,2′-bipyridine (Y2bpy; Y = H (bpy), Me, Cl, N(Et)2, CONH2 or COOEt) or 2,2′-bipyrimidine) and an aromatic amino acid (AA = l-phenylalanine (Phe), p-substituted phenylalanine (XPhe; X = NH2, NO2, F, Cl or Br), l-tyrosine (Tyr), l-tryptophan (Trp) or l-alanine (Ala)) were characterized by X-ray diffraction, spectroscopic and potentiometric measurements. The structures of [Cu(dpa)(Trp)]ClO4·2H 2O and [Cu((CONH2)2bpy)(Phe)]ClO 4·H2O in the solid state were revealed to have intramolecular π-π interactions between the Cu(ii)-coordinated aromatic ring moiety, Cu(DA) (Mπ), and the side chain aromatic ring of the AA (Lπ). The intensities of Mπ-Lπ interactions were evaluated by the stability constants of the ternary Cu(ii) complexes determined at 25 °C and I = 0.1 M (KNO3), which revealed that the stability enhancement of the Cu(DA)(AA) systems due to the interactions is in the order (CONH 2)2bpy < bpy < Me2bpy < (Et 2N)2bpy with respect to DA. The results indicate that the electron density of coordinated aromatic diimines influences the intensities of the stacking interactions in the Cu(DA)(AA) systems. The Mπ-Lπ interactions are also influenced by the substituents, X, of Lπ and are in linear relationship with their Hammett σp values with the exception of X = Cl and Br. © The Royal Society of Chemistry
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| 8.
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Ogawa, Toshikazu ; Kitoh, Sohichi ; Ichitani, Masaki ; Kuwae, Akio ; Hanai, Kazuhiko ; Kunimoto, Koki
概要:
The crystal structure of 5-phenyl-2-thioxo-4-imidazolidinone has been determined by X-ray diffraction. The crystal, C9H8
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N2OS, belongs to space group P1 with cell dimensions of a = 8.971(3)Å, b = 9.651(3)Å, c = 10.497(3)Å, α = 82.39(2)°, β = 80.15(2)°, γ = 79.16(2)°. The final R value is 0.045 for 2683 reflections (I > 2.00σ(I)). There are two independent molecules, A and B, in the asymmetric unit. The molecules differ mainly in the orientation of the phenyl ring with respect to the five-membered ring. In crystals, the thioamide groups of molecules A and B form centrosymmetric dimers A-A and B-B via the N-H…S hydrogen bonds. The amide groups of two neighboring molecules, A and B, form pseudo-centrosymmetric dimers A-B through N-H…O hydrogen bonds.
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| 9.
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論文
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Ishiura, Yoshihisa ; Fujimura, Masaki ; Nobata, Kouichi ; Oribe, Yoshitaka ; Abo, Miki ; Myou, Shigeharu
概要:
金沢大学大学院医学系研究科機能再生学<br />Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of
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prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) μM] compared with placebo [30.3 (GSEM 1.21) μM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma.
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| 10.
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論文
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Ohashi, Masashi ; Oomi, Gendo ; Satoh, Isamu
概要:
金沢大学大学院自然科学研究科環境計画<br />The magnetic susceptibility of CeNiGe2 single crystal has been measured under high pressure up t
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o 2.0 GPa. Although two anomalies are observed at TN1=4.0 K and at TN2=3.0 K at ambient pressure, TN2 disappears above 0.13 GPa, while TN1 still remains near 2.0 K up to 2.0 GPa. On the other hand, the peak height of the susceptibility curve decreases with increasing pressure, which may suggest that the correlation between conduction and f-electrons is strengthened by pressure. The Kondo temperature TK is estimated from the maximum of χc–T curve. TK is remarkably enhanced by applying pressure.
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