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Kōbe-shi, Japan

Mizushina Y.,Kobe Gakuin University | Takahashi Y.,Oguraya Yanagimoto Co. | Sato Y.,Tokyo University of Science | Yamaguchi Y.,Tokyo University of Science | And 4 more authors.
Food Chemistry | Year: 2012

During the screening of selective DNA polymerase (pol) inhibitors, we isolated two glucosyl compounds, a cerebroside (glucosyl ceramide, AS-1-4, compound 1) and a steroidal glycoside (eleutheroside A, compound 2) from soybean (Glycine max L.). Compounds 1 and 2 selectively inhibited the activity of eukaryotic pol λ in vitro, with IC 50 values of 12.2 and 9.1 μM, respectively. These compounds did not influence the activities of other eukaryotic pols including those from the A-family (pol γ), B-family (pols α, δ and ), and Y-family (pols η, ι and κ), and also showed no effect on the activity of pol β which is of the same family (X) as pol λ. The tendency for in vitro pol λ inhibition by these compounds showed a positive correlation with the in vivo suppression of TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation in mouse ear. These results suggest that these glucosyl compounds from soybean may be useful for their anti-inflammatory properties. © 2011 Elsevier Ltd. All rights reserved. Source


Mizushina Y.,Kobe Gakuin University | Takeuchi T.,Tokyo University of Science | Kuriyama I.,Kobe Gakuin University | Takahashi Y.,Oguraya Yanagimoto Co. | And 5 more authors.
Letters in Drug Design and Discovery | Year: 2011

Two mammalian DNA polymerase β (pol β) inhibitors have been isolated independently from the brown algae Laminaria sp. These molecules were determined by spectroscopic analyses to be a loliolide derivative, 2,3a-dihydroxy-4,4,6,7a-tetramethyl-3-oxo-octahydro-1-benzofuran-6-yl acetate (compound 1), and pubinernoid A (compound 2). Compounds 1 and 2 selectively inhibited the activity of rat pol β, and 50% inhibition was observed at concentrations of 18.4 and 38.8 μM, respectively. By contrast, these compounds did not influence the activity of 10 other mammalian pols [pols α, γ, δ, ε, η, l, κ, λ, μ. and terminal deoxynucleotidyl transferase (TdT)] tested, and showed no effect even on the activity of fish pol δ, plant pols α and λ, prokaryotic pols, or any other DNA or RNA metabolic enzymes tested. Inhibition of rat pol β activity by compounds 1 and 2 was competitive with both DNA template-primer and nucleotide substrate. The structure-activity relationship of these compounds is discussed. © 2011 Bentham Science Publishers Ltd. Source


Mizushina Y.,Kobe Gakuin University | Takeuchi T.,Tokyo University of Science | Kuriyama I.,Kobe Gakuin University | Takahashi Y.,Oguraya Yanagimoto Co. | And 5 more authors.
Letters in Drug Design and Discovery | Year: 2011

Two mammalian DNA polymerase β (pol β) inhibitors have been isolated independently from the brown algae Laminaria sp. These molecules were determined by spectroscopic analyses to be a loliolide derivative, 2,3a-dihydroxy-4,4,6,7a-tetramethyl-3-oxo-octahydro-1-benzofuran-6-yl acetate (compound 1), and pubinernoid A (compound 2). Compounds 1 and 2 selectively inhibited the activity of rat pol β, and 50% inhibition was observed at concentrations of 18.4 and 38.8 μM, respectively. By contrast, these compounds did not influence the activity of 10 other mammalian pols [pols α, γ, δ, ε, η, ι, κ, λ, μ. and terminal deoxynucleotidyl transferase (TdT)] tested, and showed no effect even on the activity of fish pol δ, plant pols α and λ, prokaryotic pols, or any other DNA or RNA metabolic enzymes tested. Inhibition of rat pol β activity by compounds 1 and 2 was competitive with both DNA template-primer and nucleotide substrate. The structure-activity relationship of these compounds is discussed. © 2011 Bentham Science Publishers Ltd. Source


Mizushina Y.,Kobe Gakuin University | Shiomi K.,Kobe Gakuin University | Kuriyama I.,Kobe Gakuin University | Takahashi Y.,Oguraya Yanagimoto Co. | Yoshida H.,Kobe Gakuin University
International Journal of Oncology | Year: 2013

The inhibitory activity of 3 soy isoflavones (daidzein, genistein and glycitein) and their glycosides (daidzin, genistin and glycitin) on mammalian DNA polymerases (pols) and topoisomerases (topos) was investigated. Of the compounds tested, only genistein selectively inhibited human topo II activity and had an IC50 value of 37.5 M. These isoflavones had no effect on the activity of human topo I; mammalian pols , β, and κ; or on any other DNA metabolic enzyme tested. Thermal transition analysis indicated that genistein did not influence the direct binding to double-stranded DNA. Genistein prevented the proliferation of HCT116 human colon carcinoma cells with an LD50 of 94.0 M and it halted the cell cycle in G2/M phase. These results suggest that decreases in cell proliferation due to genistein may result from the inhibition of cellular topo II and that genistein, a major soy isoflavone, may be an anticancer food component. The relationship between the structures and these bioactivities of soy isoflavones is discussed. Source

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