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31.
32.
Shigemitsu Matsumoto Naoki Miyamoto Takaharu Hirayama Hideyuki Oki Kengo Okada Michiko Tawada Hidehisa Iwata Kazuhide Nakamura Seiji Yamasaki Hiroshi Miki Akira Hori Shinichi Imamura 《Bioorganic & medicinal chemistry》2013,21(24):7686-7698
To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC50 = 1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50 = 5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C] = 4%, po, 5 mg/kg, once-daily) and COLO205 (T/C = 13%, po, 15 mg/kg, once-daily) mouse xenograft models. 相似文献
33.
Hiroko Kato Kenji Izumi Taro Saito Hisashi Ohnuki Michiko Terada Yoshiro Kawano Kayoko Nozawa-Inoue Chikara Saito Takeyasu Maeda 《Histochemistry and cell biology》2013,139(6):847-862
Aldehyde dehydrogenases (ALDHs), enzymes responsible for detoxification and retinoic acid biosynthesis, are considered a potent functional stem cell marker of normal and malignant cells in many tissues. To date, however, there are no available data on ALDH distributions and functions in oral mucosa. This study aims to clarify the levels and types of ALDH expression using immunohistochemistry with accompanying mRNA expression as well as an ALDEFLUOR assay, and to assess phenotypic and histological changes after manipulation of the ALDH activity of oral keratinocytes to increase the potency of a tissue-engineered oral mucosa by a specific ALDH inhibitor, diethylaminobenzaldehyde (DEAB), together with small interfering RNA of ALDH1A3 and ALDH3A1. Results showed the mRNA and cytoplasmic protein expression of ALDH1A3 and ALDH3A1 to be mostly localized in the upper suprabasal layer although no ALDH1A1 immunoreaction was detected throughout the epithelium. Oral keratinocytes with high ALDH activity exhibited a profile of differentiating cells. By pharmacological inhibition, the phenotypic analysis revealed the proliferating cell-population shifting to a more quiescent state compared with untreated cells. Furthermore, a well-structured epithelial layer showing a normal differentiation pattern and a decrease in Ki-67 immunopositive basal cells was developed by DEAB incubation, suggesting a slower turnover rate efficient to maintain undifferentiated cells. Histological findings of a regenerated oral epithelium by ALDH1A3 siRNA were similar to those when treated with DEAB while ALDH3A1 siRNA eradicated the epithelial regenerative capacity. These observations suggest the effects of phenotypic and morphological alterations by DEAB on oral keratinocytes are mainly consequent to the inhibition of ALDH1A3 activity. 相似文献
34.
Tei Yamanishi Michiko Kosuge Yukiko Tokitomo Ryoko Maeda 《Bioscience, biotechnology, and biochemistry》2013,77(9):2139-2142
The aroma constituents of the highest quality pouchong tea were characterized by GC–MS. Forty-eight components, including five newly identified compounds were characterized. GC peak area percentages of the main components in pouchong tea were compared with those of jasmine tea to differentiate compounds contributing to the aroma characteristics of pouchong tea with superior floral elegant flavor. Nerolidol, jasmine lactone, methyl jasmonate, indole, benzyl cyanide and linalool oxides were found in much higher concentration in pouchong tea than in jasmine tea. These compounds seemed to contribute to the aroma characteristics of the highest quality pouchong tea. 相似文献
35.
Soichi Arai Michiko Yamashita Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(7):1253-1256
AK-toxin I, a host-specific toxin to Japanese pear (Pyrus serotina), was synthesized as its methyl ester from three precursor fragments: conjugated diene-carboxylic acid, chiral epoxyalcohol and β-methylphenylalanine. The epoxyalcohol fragment was derived from D-fructose, in which effective homologation of the hemiacetal carbon to alkyne by using dimethyl 1-diazo-2-oxopropylphosphonate was the key reaction. The diene-carboxylic acid fragment was prepared by repeated Wittig reactions, and was combined with the epoxyalcohol fragment by the Stille reaction. Esterification of the combined product with the stereochemically-pure β-methylphenylalanine fragment afforded the target compound. This method was used to prepare the methyl ester of tritium-labeled AK-toxin I with a specific radioactivity of 213 GBq/mmol. 相似文献
36.
Satoshi Ōmura Michiko Katagiri Juichi Awaya Kiyoo Atsumi Ruiko Ōiwa Toju Hata 《Bioscience, biotechnology, and biochemistry》2013,77(12):2805-2812
A newly described species of Streptomyces (named Sm. kagawaensis ATCC No. 21811) isolated from soil was found to produce a new antifungal antibiotic, prumycin, which belongs to amino sugar group. Prumycin was isolated from the fermentation broth by ion-exchange adsorption and gel-filtration methods. This antibiotic inhibited specifically the growth of Sclerotinia sp. and Botrytis sp. on flower pot test with kidney bean leaves and also was effective on the field test with various plants. 相似文献
37.
Shin-ya Tanimoto Michiko Yamashita Soichi Arai Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):1595-1602
A plastein was synthesized with α-chymotrypsin from a dialyzable fraction of a peptic hydrolysate of soybean protein.The plastein was obtainable also by use of an insoluble preparation of α-chymotrypsin. This may rule out the possibility that the plastein is a product resulting from some chemical peptide-protein (enzyme) aggregation.No appreciable amount of the plastein was produced when chymotrypsinogen was used instead of α-chymotrypsin.The plastein synthetic, as well as the protein hydrolytic, activity of α-chymotrypsin was inhibited more or less by a hydrophobic inhibitor (n-hexane), a competitive inhibitor (benzolyl-d,l-phenylalanine), and divalent cations (Zn2+, Hg2+ and Cu2+); the degree of inhibition in each case was approximately similar against both the synthetic and the hydrolytic activities.Either diisopropylphosphorylation of the β-O of Ser-195 or methylation of the 3-N of His-57 imidazole of α-chymotrypsin repressed the synthetic, as well as the hydrolytic, activity.Based on these results a possible mechanism was discussed of the plastein synthesis by α-chymotrypsin, especially in relevance to its acylation and deacylation. 相似文献
38.
Michiko Nose Yoichi Nakatani Tei Yamanishi 《Bioscience, biotechnology, and biochemistry》2013,77(2):261-271
By continuing flavor analysis of green tea from a previous paper, further twenty seven compounds were newly identified. These compounds are limonene, α-cubebene, α-copaene, caryophyllene, α-humulene, α- and γ-muurolene, β-sesquiphellandrene, δ-cadinene, calamenene, cubenol, α-cadinol, α-terpineol, n-heptanol, n-nonanol, furfurylalcohol, n-nonanal, N-ethylformylpyrrole, pyrrylmethylketone, 6-methyl-trans-3,5-heptadien-2-one, 2′,2″-dihydro-α-ionone, 6,10,14-trimethyl-2-pentadecanone, cis-3-hexenylcaproate, cis-3-hexenylbenzoate, α-terpinylacetate, coumarin and diphenylamine.Relative quantities of known compounds in intermediate- and high-boiling fraction were determined. 相似文献
39.
Soichi Arai Makoto Abe Michiko Yamashita Hiromichi Kato Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(4):552-559
An indole derivative having blue fluorescence was produced in cooked soybean digested at 37°C for 24 hr with an acid proteinase Molsin (optimum pH: 2.8) from Aspergillus saitoi or a usual acid proteinase pepsin (optimum pH: 1.6) from beef stomach. This indole derivative was identical with a condensation product from l-tryptophan and n-hexanal. Based on MS, NMR, IR and UV spectrometry, the condensation product was identified as l-pentyl-2, 3, 4, 9-tetrahydro-lH-pyrido [3, 4-b]-indole-3-carboxylic acid [trivial name: 1-pentyl-l, 2, 3, 4-tetrahydro-2-carboline carboxylic acid-(3)].Data were presented of the formation of the above indole derivative and of the resulting consumption of l-tryptophan and n-hexanal.The possible ocurrence of the formation of Harmala alkaloids, i.e. 2-carboline derivatives, through in vitro digestion of soybean with acid proteinases was discussed.A carbonyl-trapping ability of l-tryptophan was suggested. 相似文献
40.
Soichi Arai Masatoshi Noguchi Michiko Yamashita Hiromichi Kato Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(9):1338-1345
Soy proteins were incubated with a microbial acid protease (Molsin) under the following condition: substrate concentration, 1%; enzyme-substrate ratio (by weight), 1/100; pH, 2.8; and temperature, 40°C—flavor components and related impurities are removable from crude soy-protein concentrates by their incubation for 2 hr under the above condition. The acid-precipitated fraction of soy protein incubated for 2 hr with Molsin (i.e. 2 hr-proteolyzate) showed the following composition: 10% trichloroacetic acid (TCA) insoluble fraction, 47.52%; 10% TCA soluble peptide fraction, 52.02%; and free amino acid fraction, 0.46%. Gel filtration of the 2 hr-proteolyzate gave an elution pattern showing its molecular weight distribution.In the process of the incubation of the acid-precipitated protein, the 10% TCA insoluble fraction showed increase in amino nitrogen content, its solubility in a phosphate buffer increased to change at 6 hr, and a hydrophobic amino acid share in this fraction increased gradually.In vitro digestibility of the acid-precipitated fraction were improved and the lipoxygenase activity in this fraction decreased through the Molsin treatment.Ultracentrifugal analysis showed a decreasing tendency of the cold-insoluble fraction of soy protein during its incubation with Molsin. Optical rotatory dispersion and circular dichroism study elucidated conformational changes in this fraction during its incubation either with or without Molsin. 相似文献