Reviews, Commentaries, etc. - Arai, Midori

E3ユビキチンリガーゼプレートを用いた天然物由来tau分解分子糊の探索

遠周 直人, 林 愛菜, 齋藤 駿, 荒井 緑

日本生薬学会年会講演要旨集 ((一社)日本生薬学会)  68回   197 - 197 2022.08

ISSN  0919-1992

Notchシグナル不活性型がんを標的とした微生物由来治療薬シードの探索

鈴木 しいな, 齋藤 駿, 蒔田 吉功, 新家 一男, 荒井 緑

日本生薬学会年会講演要旨集 ((一社)日本生薬学会)  68回   216 - 216 2022.08

ISSN  0919-1992

病原真菌と免疫細胞の共培養法を用いた休眠遺伝子活性化による新規天然物の探索

氏江 優希子, 齋藤 駿, 矢口 貴志, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27PO1 - am2 2022.03

ISSN  0918-9823

耐熱性放線菌JA74株が生産する熱ショック代謝物maniwamycin類の全合成及び生物活性評価

船山 佳世, 齋藤 駿, 加藤 航, 新藤 一敏, 川本 芽子, 松原 輝彦, 佐藤 智典, 乙黒 聡子, 前仲 勝実, 井本 正哉, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27T - am06S 2022.03

ISSN  0918-9823

腸内細菌が生産する代謝物からの免疫機能制御物質の探索

坂野 智也, 齋藤 駿, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27PO7 - pm1 2022.03

ISSN  0918-9823

高活性Notchシグナル阻害剤を目指したaciculatin誘導体の創製

成島 悠貴, 林 奈留美, 蒔田 吉功, 石橋 正己, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27PO5 - pm2 2022.03

ISSN  0918-9823

Ascl1発現阻害作用を有するヘテロ環含有ロカグラミド誘導体の創製(第2報)

蒔田 吉功, 齋藤 駿, 石橋 正己, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27S - pm23S 2022.03

ISSN  0918-9823

FBW7プレートを用いたtau分解天然分子糊の探索

遠周 直人, 林 愛菜, 齋藤 駿, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27PO1 - am1 2022.03

ISSN  0918-9823

抗がん剤シードを目指した微生物由来Notchシグナル活性化剤の探索

鈴木 しいな, 齋藤 駿, 蒔田 吉功, 新家 一男, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27T - am04S 2022.03

ISSN  0918-9823

乳酸菌と動物細胞の共培養による有用物質の探索

細内 梨央, 齋藤 駿, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  142年会   27PO1 - am1 2022.03

ISSN  0918-9823

病原真菌Aspergillus属と免疫細胞の共培養法を用いた新規天然物の探索

桑原 るり, 原 康雅, 荒井 緑, 矢口 貴志, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  141年会   28P01 - 042S 2021.03

ISSN  0918-9823

Ascl1発現阻害作用を有するヘテロ環含有ロカグラミド誘導体の創製

蒔田 吉功, 石橋 正己, 荒井 緑

日本薬学会年会要旨集 ((公社)日本薬学会)  141年会   28P02 - 053S 2021.03

ISSN  0918-9823

Spirit of south countrywoman in research

Arai M.A

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry (Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry)  79 ( 1 ) 56 - 58 2021.01

ISSN  00379980

• Access to Document (DOI)
• CiNii Research

Andrographis paniculataからのBMI1プロモーター阻害作用を示す天然物の探索

藤井 一樹, 荒井 緑, 原 康雅, Sadhu Samir K., Ahmed Firoj, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   27L - pm08S 2020.03

ISSN  0918-9823

Notchシグナル阻害作用を有するスピロオキシインドール誘導体の創成研究

川野 はるか, 荒井 緑, 荒井 孝義, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28K - pm14S 2020.03

ISSN  0918-9823

Santalum albumからのWntシグナル阻害化合物の探索

佐藤 知幸, 荒井 緑, 原 康雅, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   27L - pm09S 2020.03

ISSN  0918-9823

病原放線菌Nocardia属薬剤耐性菌株からの生物活性天然物の探索

海老原 樹, 荒井 緑, 原 康雅, 矢口 貴志, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28Q - pm140S 2020.03

ISSN  0918-9823

新規肺高血圧症治療薬を目指したHIF-1阻害剤の探索

櫻庭 康太, 荒井 緑, 坂尾 誠一郎, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   27L - pm03S 2020.03

ISSN  0918-9823

放線菌からのTRAIL耐性がん細胞に毒性を示す化合物の探索

市川 展史, 原 康雅, 荒井 緑, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28Q - pm128S 2020.03

ISSN  0918-9823

動物細胞との共培養法による病原性放線菌Nocardia属由来新規生物活性天然物の探索

原 康雅, 荒井 緑, 矢口 貴志, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   28Q - pm138 2020.03

ISSN  0918-9823

動物細胞との共培養による病原放線菌Nocardia属からの免疫抑制化合物の探索

谷村 大樹, 荒井 緑, 原 康雅, 矢口 貴志, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   27L - pm10S 2020.03

ISSN  0918-9823

センダン科植物からのロカグラミド関連天然物の探索

野崎 はるか, 荒井 緑, 蒔田 吉功, 市川 展史, 原 康雅, Sadhu Samir K., Ahmed Firoj, 小谷野 喬, Thaworn Kowithayakorn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   27P - pm224S 2020.03

ISSN  0918-9823

TRAIL耐性克服作用を有するヘテロ環含有ロカグラミド誘導体の創製

蒔田 吉功, 荒井 緑, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  140年会   26P - am105S 2020.03

ISSN  0918-9823

Synthesis of neural stem cells activator: lindbladione

牧田祐奈, 牧田祐奈, 荒井緑, 荒井緑, 石橋正己, 石橋正己

日本薬学会年会要旨集(CD-ROM) 140th (Web) 2020

生死の天秤シグナルを制御する天然基盤小分子の創成

荒井 緑

上原記念生命科学財団研究報告集 ((公財)上原記念生命科学財団)  33   1 - 5 2019.12

Santalum albumからのWntシグナル阻害作用をもつ天然物の探索

佐藤知幸, 荒井緑, 原康雅, 益西卓瑪, 小谷野喬, KOWITHAYAKORN Thaworn, 石橋正己

日本生薬学会年会講演要旨集 66th   217 2019.08

ISSN  0919-1992

新規肺高血圧症治療薬を目指したHIF‐1阻害剤の探索

櫻庭康太, 荒井緑, 坂尾誠一郎, 石橋正己

日本生薬学会年会講演要旨集 66th   190 2019.08

ISSN  0919-1992

Notchシグナル阻害作用を有する光学活性スピロオキシインドール誘導体の創成研究

荒井緑, 荒井緑, 川野はるか, 荒井孝義, 荒井孝義, 荒井孝義, 石橋正己, 石橋正己

シンポジウム「モレキュラー・キラリティー」講演要旨集 2019   136‐137 2019.06

ISSN  1881-0861

Hes1二量体形成阻害活性を有する天然物の探索

盛田かおり, 荒井緑, SADHU Samir K, AHMED Firoj, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.21PO‐pm066S 2019

神経幹細胞分化活性化剤lindbladioneの全合成研究

牧田祐奈, 荒井緑, 山口祐未, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.23PO‐pm010S 2019

放線菌からのBMI1プロモーター阻害作用をもつ天然物の探索

横山夕将, 荒井緑, 原康雅, 石橋正己

食品薬学シンポジウム講演要旨集 8th (Web) 2019

千葉化合物ライブラリーからのAscl1発現モジュレーターの創製

本山あゆみ, 荒井緑, 荒井孝義, 影山龍一郎, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.22PO‐am105S 2019

ヘテロ環含有ロカグラミド誘導体の合成と生物活性評価

蒔田吉功, 荒井緑, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.22PO‐am109S 2019

タイ産植物からのWntシグナルに作用する天然物の探索

佐藤知幸, 荒井緑, 益西卓瑪, 小谷野喬, KOWITHAYAKORN Thaworn, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.23T‐pm10S 2019

Streptomyces sp.IFM11958などからのBMI1プロモーター阻害剤の探索

横山夕将, 荒井緑, 原康雅, 石橋正己

日本薬学会年会要旨集(CD-ROM) 139th   ROMBUNNO.22O‐pm18S 2019

センダン科植物によるrocaglamide関連天然物の探索

野崎はるか, 荒井緑, SADHU Samir K, AHMED Firoj, 小谷野喬, KOWITHAYAKORN Thaworn, 石橋正己

日本生薬学会年会講演要旨集 65th   163 2018.08

ISSN  0919-1992

放線菌二次代謝産物からのBMI1プロモーター阻害剤の探索

横山夕将, 荒井緑, 石橋正己

日本生薬学会年会講演要旨集 65th   50 2018.08

ISSN  0919-1992

神経再生医薬を目指したスピロ型Notchシグナル阻害剤の創製

荒井緑, 荒井緑, 岡野美優, 川野はるか, 荒井孝義, 荒井孝義, 石橋正己, 石橋正己

複素環化学討論会講演要旨集 48th   147 2018.08

細胞シグナルに作用する生物活性植物成分のスクリーニング研究

石橋正己, 荒井緑

日本ポリフェノール学会雑誌 (日本ポリフェノール学会)  7 ( 1 ) 6‐12 - 12 2018.06

ISSN  2187-1175

NICDビーズを用いたNotchシグナル阻害剤の探索

林 奈留美, 荒井 緑, 菅波 晃子, 田村 裕, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  138年会 ( 2 ) 97 - 97 2018.03

ISSN  0918-9823

リグナン骨格を有する神経幹細胞分化促進剤の創成研究

三瓶 真菜, 荒井 緑, 菅波 晃子, 田村 裕, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  138年会 ( 2 ) 115 - 115 2018.03

ISSN  0918-9823

Amonum villosum等からのTRAIL耐性克服作用を持つ天然物の探索

石川龍翔, PRAPAIRAT Seephonkai, PRAPAIRAT Seephonkai, 荒井緑, SAMIR K. Sadhu, FIROJ Ahmed, 小谷野喬, THAWORN Kowithayakorn, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am273S 2018

放線菌Nocardia属からの新規二次代謝産物の探索

小林菜摘, 原康雅, 荒井緑, 五ノ井透, 矢口貴志, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am256S 2018

放線菌二次代謝産物からのBMI1プロモーター阻害剤の探索

横山夕将, 荒井緑, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am255S 2018

Beaumontia murtoniiなどからのBMI1プロモーター阻害剤の探索及び活性評価

金田結, 石川直樹, 荒井緑, 當銘一文, 小谷野喬, KOWITHAYAKORN Thaworn, 千葉哲博, 岩間厚志, 石橋正己

天然薬物の開発と応用シンポジウム講演要旨集 21st   105‐107 2016.10

ISSN  0919-2085

Polyalthia cerasoidesからのWntシグナル阻害する新規アルカロイド

庄野 巧, 石川 直樹, 當銘 一文, 荒井 緑, 枡 飛雄真, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本生薬学会年会講演要旨集 ((一社)日本生薬学会)  63回   179 - 179 2016.08

ISSN  0919-1992

Polyalthia cerasoidesからのWntシグナルを阻害する天然物の探索

庄野 巧, 石川 直樹, 當銘 一文, 荒井 緑, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 124 - 124 2016.03

ISSN  0918-9823

TRAIL耐性克服作用を有するFuligocandin Bの標的タンパク質同定と作用機序解析に向けた研究

荒井 緑, 田口 翔大, 佐藤 守, 荷堂 清香, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 117 - 117 2016.03

ISSN  0918-9823

ヒストン修飾に関わるポリコーム構成分子BMI1を標的とした天然物の探索

金田 結, 石川 直樹, 當銘 一文, 荒井 緑, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 59 - 59 2016.03

ISSN  0918-9823

Target Identification and Mode of Action of 5'-I Fuligocandin B with TRAIL-resistance Overcoming Activity

Arai Midori A., Taguchi Shota, Komatsuzaki Kazuhiro, Uchiyama Kento, Masuda Ayaka, Satoh Mamoru, Kado Sayaka, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  58 ( 0 ) Oral15 2016

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<p> Fuligocandin A (1) and B (2) are novel natural cycloanthranilylproline derivatives isolated from Fuligo candida. We found the ability of 2 to overcome TRAIL-resistance of cancer cells. Enatiometically pure Fuligocandin B (2) and its derivative 5'-I Fuligocandin B (9) were synthesized, and the latter had an improved TRAIL-resistance overcoming activity against AGS cells. A biotin probe of 9 that had a photo-activatable aryl diazirine group was synthesized, and a pull-down assay revealed that Valosin-containing protein (VCP/p97), an AAA+ ATPase, was a target protein of 9. Knock-down of VCP by siRNA enhanced sensitivity to TRAIL in AGS cells. In addition, 9 enhanced ubiqutination of proteins and CHOP expression, which was a regulator of DR5. These data suggest that ER stress caused by VCP inhibition by 9 increases CHOP-mediated DR5 up regulation, which enhances TRAIL induced cell death. To the best of our knowledge, this is the first experimental data linking VCP and TRAIL-resistance overcoming activity in cancer cells. </p>

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Hibiscus ficulneusからのWntシグナル阻害作用をもつ天然物の探索

SHONO TAKUMI, ISHIKAWA NAOKI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR KUMAR, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 135th   ROMBUNNO.27PB-PM168 2015

Search for activator of neural stem cells differentiation based on inhibition of Notch-Hes signaling pathway

Arai Midori.A, Akamine Ryuta, Yoneyama Tatsuro, Okamoto Ryuichi, Koyano Takashi, Kowithayakorn Thaworn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  57 ( 0 ) PosterP1 2015

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<p> Basic helix-loop-helix (bHLH) repressor- and activator-type transcription factors play essential roles in proliferation and differentiation of neural stem cells (NSCs). Hes1 and Hes5, bHLH repressor-type factors, lead NSCs to remaining undifferentiation. The transcription of Hes1 and Hes5 are regulated by Notch signaling pathway. Therefore, inhibition of Notch signaling pathway would accelerate NSCs differentiation into neurons and glial cells. To find inhibitors of Notch signaling pathway from natural resources, we constructed a cell-based reporter assay of NICD-mediated transcription.</p><p>By using this assay system, we isolated twelve xanthones (1-12) including a new compound (12) from Garcinia speciosa (bark). Structure of 12was elucidated by spectroscopic data analyses. Among the isolated compounds, 2strongly inhibited the transcriptional activity of NICD. Western blot analysis of 2showed decrease in Hes1 and Hes5 protein expression. NICD was also decreased, but NotchDE was increased. These results suggested that 2inhibits Notch signaling pathway by the inhibition of g-secretase.</p><p> Five cardenolide glycosides (13-17) were isolated from Nerium indicum (leaves). 13inhibited the transcriptional activity of NICD with IC₅₀ values of 0.12 mM. Western blot analysis of 13showed decrease in Hes1 and Hes5 protein expression. Uscharin (18) and calotropin (19) were also found as Notch signaling inhibitors. Next, we examined the effect of 13, 18 and 19on NSCs differentiation. These compounds accelerated differentiation of mouse NSCs (MEB5) into neurons and glial cells.</p>

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Search for activator of neural stem cells differentiation based on inhibition of Notch-Hes signaling pathway

Arai Midori.A, Akamine Ryuta, Yoneyama Tatsuro, Okamoto Ryuichi, Koyano Takashi, Kowithayakorn Thaworn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  57 ( 0 )  2015

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&lt;p&gt; Basic helix-loop-helix (bHLH) repressor- and activator-type transcription factors play essential roles in proliferation and differentiation of neural stem cells (NSCs). Hes1 and Hes5, bHLH repressor-type factors, lead NSCs to remaining undifferentiation. The transcription of Hes1 and Hes5 are regulated by Notch signaling pathway. Therefore, inhibition of Notch signaling pathway would accelerate NSCs differentiation into neurons and glial cells. To find inhibitors of Notch signaling pathway from natural resources, we constructed a cell-based reporter assay of NICD-mediated transcription.&lt;/p&gt;&lt;p&gt;By using this assay system, we isolated twelve xanthones (1-12) including a new compound (12) from Garcinia speciosa (bark). Structure of 12was elucidated by spectroscopic data analyses. Among the isolated compounds, 2strongly inhibited the transcriptional activity of NICD. Western blot analysis of 2showed decrease in Hes1 and Hes5 protein expression. NICD was also decreased, but NotchDE was increased. These results suggested that 2inhibits Notch signaling pathway by the inhibition of g-secretase.&lt;/p&gt;&lt;p&gt; Five cardenolide glycosides (13-17) were isolated from Nerium indicum (leaves). 13inhibited the transcriptional activity of NICD with IC&lt;sub&gt;50&lt;/sub&gt; values of 0.12 mM. Western blot analysis of 13showed decrease in Hes1 and Hes5 protein expression. Uscharin (18) and calotropin (19) were also found as Notch signaling inhibitors. Next, we examined the effect of 13, 18 and 19on NSCs differentiation. These compounds accelerated differentiation of mouse NSCs (MEB5) into neurons and glial cells.&lt;/p&gt;

Tabernaemontana divaricataからのWntシグナルを阻害する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, SAMIR K SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 135th   ROMBUNNO.27PB-PM210S 2015

Eurycoma longifolia等からのWntシグナルを阻害する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, MIZOGUCHI TAKAMASA, ITO MOTOYUKI, SADHU SAMIR K, AHMED FIROJ, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

天然薬物の開発と応用シンポジウム講演要旨集 20th   69 - 71 2014.11

ISSN  0919-2085

Artocarpus communis由来のTRAIL耐性克服作用をもつプレニルフラボン成分

HABU TADASHI, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

香料・テルペンおよび精油化学に関する討論会講演要旨集 58th   307 - 309 2014.09

Hibiscus ficulneusからのWntシグナル阻害作用を持つ天然物の探索

SHONO TAKUMI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 61st   181 2014.08

ISSN  0919-1992

Search for bioactive natural products that inhibit Wnt signaling pathway from Calotropis giantea and Xylocarpus granatum

Toume Kazufumi, Park Hyun Young, Kamiya Kentaro, Arai Midori, Samir K. Sadhu, Firoj Ahmed, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  56 ( 0 )  2014

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&lt;p&gt;Wnt signaling pathway has a key roles in various cellular process such as cell proliferation and tissue maintenance. Aberrant activation of Wnt signal can initiate the development of several diseases including cancer, Alzheimer&#039;s disease, and diabetes. Using cell-based luciferase screening assay system for a Wnt signaling pathway (TCF/β-catenin transcription), activity-guided exploration of our natural resources extracts library were conducted. Detailed investigation on mode of action of isolated compounds were also carried out.&lt;/p&gt;&lt;p&gt;Six cardenolides (1-6) were isolated from the methanol extract of Calotropis gigantea (Asclepiadaceae) exudate, and compounds 1, 3, 5, and 6 strongly inhibited TCF/β-catenin transcription activity (IC&lt;sub&gt;50&lt;/sub&gt;0.7-3.8 nM). Compounds 1, and 3-6showed potent cytotoxicity (IC&lt;sub&gt;50&lt;/sub&gt; 1.8-7.0 nM) against Wnt dependent colon cancer cell (SW480, DLD1, HCT116), without cytotoxicity against RKO (Wnt independent colon cancer) cells. Calotropin (1) inhibited Wnt signaling by reducing both nuclear and cytosolic β-catenin levels in SW480 cells. Further investigation using inhibitors revealed that 1 potentiate the degradation of β-catenin by increasing the phosphorylation of β-catenin at Ser45 mediated by casein kinase 1α (CK1α). Moreover, 1 significantly enhanced CK1α protein and mRNA levels.&lt;/p&gt;&lt;p&gt;Three limonoides (7-9) were isolated from methanol extract of Xylocarpus granatum (Meliaceae) leaves, including two new limonoids, named as xylogranin A (7) and B (8). Compounds 7 and 8 inhibited TCF/β-catenin transcription activity. Treatment of SW480 cells with 8 led to a significant decrease of β-catenin in nuclei but not in the cytosol, and c-myc and PPARδ, target proteins of Wnt signaling pathway. These results indicated that a decrease of β-catenin in nuclei by 8contributed the Wnt inhibition of 8.&lt;/p&gt;

Calotropis gigantea由来カルデノリドCalotropinのウィントシグナル阻害作用

BOKU KEN'EI, TOUME KAZUFUMI, ARAI MIDORI, SAMIR K. SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 134th   ROMBUNNO.29AMM-126 2014

Artocarpus communis由来プレニルフラボノイドのTRAIL耐性克服作用

HABU OSAMU, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 134th   ROMBUNNO.28M-AM05S 2014

Ricinus communisなどからのWntシグナルに作用する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, MIZOGUCHI TAKAMASA, ITO MOTOYUKI, SAMIR K SADHU, FIROJ AHMED, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 134th   ROMBUNNO.28L-AM06 2014

Artocarpus communisからのTRAIL耐性克服作用を有する天然物の探索

HABU TADASHI, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

食品薬学シンポジウム講演要旨集 5th   154 - 156 2013.10

Ricinus communisからのWntシグナル活性化作用をもつ天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

食品薬学シンポジウム講演要旨集 5th   151 - 153 2013.10

Calotropis gigantea由来カルデノリドのWnt阻害作用

BOKU KEN'EI, TOUME KAZUFUMI, ARAI MIDORI, SAMIR K. SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 133rd   ROMBUNNO.29L-PM05 2013

Saussurea hypoleucaからのTRAIL耐性克服作用を有する天然物の探索

TSUCHII OSAMU, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 133rd   ROMBUNNO.28M-AM09S 2013

Zanthoxylum rhetsaからのWntシグナルを活性化する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 133rd   ROMBUNNO.29AMA-266 2013

Xylocarpus granatumの新規リモノイドのWntシグナル阻害作用

KAMIYA KENTARO, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 133rd   ROMBUNNO.29AMA-280 2013

Rapid Search for Bioactive Natural Products using Stem Cell Transcription Factor Hes1 Beads

Arai Midori A., Ishikawa Naoki, Koyano Takashi, Thaworn Kowithayakorn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  55 ( 0 ) Oral17 2013

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<p>Basic helix-loop-helix (bHLH) repressor- and activator-type transcription factors play essential roles in proliferation and differentiation of neural stem cells (NSCs). Hes1, one of bHLH repressor-type factors, suppresses transcriptions of bHLH activator-type factors such as Mash1 by binding to their promoter regions as homodimers, which leads NSCs to remaining undifferentiation. Therefore, inhibition of Hes1 dimer formation would accelerate NSCs differentiation into neurons and glial cells. To quickly find ligands of bHLH factors from natural products extracts, we constructed Hes1 immobilized sepharose beads-HPLC method. Flavonoid glycosides (1-3), xanthone derivative (4) and polyene macrololactam (5) were isolated rapidly by this method.</p><p>Compound 1 disrupted Hes1 dimer formation in mouse embryo fibroblast cells (C3H10T1/2), and moreover, 1 suppressed Hes1-mediated repression of bHLH activator-type transcription factor dose-dependently (reporter assay). In differentiation of mouse neural stem cells (MEB5), neurite outgrowth enhancement by 1 was clearly observed. The expression of pro-neural genes (activator-type bHLH transcription genes) such as Mash1 and NeuroD were increased by treatment of MEB5 with 1compared with those of control. These results suggested that the inhibition of Hes1 dimer formation by 1 would greatly contribute its mode-of-action. </p><p>Compound 4 inhibited Hes1-mediated suppression of gene expression in reporter assay, although Hes1 dimer inhibition was not detected. The mechanism of 4 would be different with that of 1.</p>

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TRAIL耐性克服作用をもつ天然物の探索:Artocarpus champedenのプレニルフラボン成分

MINAKAWA TOMOHIRO, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

香料・テルペンおよび精油化学に関する討論会講演要旨集 56th   331 - 333 2012.10

Calotropis giganteaからのWntシグナル阻害作用をもつカルデノリド

PARK HYUN, YOUNG, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

天然薬物の開発と応用シンポジウム講演要旨集 19th   88 - 90 2012.10

ISSN  0919-2085

Xylocarpus granatumからのWntシグナル阻害作用をもつ天然化合物の探索

KAMIYA KENTARO, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

天然薬物の開発と応用シンポジウム講演要旨集 19th   85 - 87 2012.10

ISSN  0919-2085

Artocarpus communis等からのTRAIL耐性克服作用を有する天然物の探索

HABU OSAMU, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN THAWORN, SAMIR SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 59th   155 2012.08

ISSN  0919-1992

Calotropis gigantea由来のWntシグナル阻害するカルデノライド

BOKU KEN'EI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 59th   220 2012.08

ISSN  0919-1992

Xylocarpus granatum由来のWntシグナル阻害作用をもつ新規リモノイド

KAMIYA KENTARO, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 59th   222 2012.08

ISSN  0919-1992

Artocarpus champedenからのTRAIL耐性克服作用を有する天然物の探索

MINAGAWA TOMOHIRO, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集 132nd ( 2 ) 174 2012.03

ISSN  0918-9823

Artocarpus communisからのTRAIL耐性克服作用を有する天然物の探索

TSUCHIO OSAMU, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集 132nd ( 2 ) 174 2012.03

ISSN  0918-9823

Wntシグナル阻害作用をもつXylocarpus granatum由来の新規リモノイド

KAMIYA KENTARO, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集 132nd ( 2 ) 173 2012.03

ISSN  0918-9823

8 New Bioactive Aromatic Heterocycles from Streptomyces spp. Collected in Chiba(Oral Presentation)

Abdelfattah Mohamed S., Toume Kazufumi, Arai Midori A., Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  54 ( 0 ) 43 - 48 2012

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During our studies on search for bioactive natural products from various sources, we have investigated bioactive metabolites of actinomycete strains collected several places in Chiba area, and isolated new bioactive aromatic heterocyclic natural products, including izumiphenazines A-D (1-4) from the cultured broth of Streptomyces sp. IFM 11204 isolated soil sample of Izumi-forest in Chiba city, izuminosides A-C (9-11) from Streptomyces sp. IFM 11260 collected also in Izumi-forest in Chiba city, new pyranonaphthoquinones (12-15) yorophenazine (16), and yoropyrazone (17) from Streptomyces sp. IFM 11307 collected from Yoro-valley, and katorazone (18) from Streptomyces sp. IFM 11299 collected from Katori city. The structures of new compounds were elucidated on the basis of spectral data, and their TRAIL resistance overcoming activity was evaluated to reveal that compound 12 at 0.1 μM proved to be the most active in this series, with 33% decrease in cell viability in the presence of TRAIL (100 ng/mL).

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ピロン環およびビスインドール骨格を含む変形菌の化学成分

ISHIBASHI MASAMI, SHINTANI AKINORI, TOUME KAZUFUMI, ARAI MIDORI

複素環化学討論会講演要旨集 41st   356 - 357 2011.09

Calotropis giganteaからのWntシグナル阻害作用をもつ天然物の探索

BOKU KEN'EI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 58th   216 2011.09

ISSN  0919-1992

Kandelia candelからのTRAIL耐性克服作用を有する天然物の探索

MINAKAWA TOMOHIRO, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 58th   139 2011.09

ISSN  0919-1992

Xylocarpus granatumからのWntシグナル阻害作用をもつ天然物の探索

KAMIYA KENTARO, MORI NAOMI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 58th   138 2011.09

ISSN  0919-1992

放線菌からのWntシグナル阻害作用をもつ天然物の探索

TAMAI YUMI, TOUME KAZUFUMI, ARAI MIDORI, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 58th   215 2011.09

ISSN  0919-1992

ウィントシグナルを制御する天然物の探索

TOUME KAZUFUMI, ARAI MIDORI, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 58th   39 - 40 2011.09

ISSN  0919-1992

Cynometra ramifloraからのデスレセプター誘導作用を有する天然物の探索

TOUME KAZUFUMI, KURNIA DIKDIK, HOQUE TAHMINA, SADHU SAMIR K, AHMED FIROJ, ARAI MIDORI, ISHIBASHI MASAMI

日本薬学会年会要旨集 131st ( 2 ) 250 2011.03

ISSN  0918-9823

Kandelia candelからのTRAIL耐性克服作用を有する天然物の探索

MINAGAWA TOMOHIRO, TOUME KAZUFUMI, AHMED FIROJ, SADHU SAMIR, ARAI MIDORI, ISHIBASHI MASAMI

日本薬学会年会要旨集 131st ( 2 ) 84 2011.03

ISSN  0918-9823

Euphorbia neriifoliaからのデスレセプター誘導作用を有する天然物の探索

HOQUE TAHMINA, NAKAZAWA TAKAFUMI, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集 131st ( 2 ) 250 2011.03

ISSN  0918-9823

Xylocarpus granatumからのWntシグナル阻害作用をもつ天然物の探索

KAMIYA KENTARO, MORI NAOMI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集 131st ( 2 ) 84 2011.03

ISSN  0918-9823

放線菌からのWntシグナル阻害作用を持つ天然物の探索

TAMAI YUYA, TOUME KAZUFUMI, ARAI MIDORI, ISHIBASHI MASAMI

日本薬学会年会要旨集 131st ( 2 ) 85 2011.03

ISSN  0918-9823

2.変異VDR(Arg274Leu)に対するセコステロイドリガンドの設計と合成(第329回会議研究発表要旨,脂溶性ビタミン総合研究委員会)

本澤 忍, 角田 真二, 齋藤 博, 高木 健一郎, 上村 みどり, 石塚 誠一, 竹之内 一弥, 榊 利之, 加藤 茂明, 栗原 正明, 高橋 尚志, 山本 康弘, 荒井 緑, 高野 真史, 澤田 大介, 山下 純, 杉浦 隆之, 橘高 敦史

ビタミン (公益社団法人 日本ビタミン学会)  85 ( 3 ) 166 - 167 2011

ISSN  0006-386X

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P-25 Search for Neural Stem Cells Activators based on Natural Products(Poster Presentation)

Arai Midori A., Koryudzu Kazune, Yanase Natsuki, Ishikawa Naoki, Koyano Takashi, Kowithayakorn Thaworn, ishibahi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  53 ( 0 ) 343 - 348 2011

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Neural stem cells (NSCs) can differentiate to neural cells such as neurons and astrocytes, therefore regenerative medicine based on natural products are urgent to neural diseases. We recently focused on the basic helix-loop-helix (bHLH) transcriptional factors, which control proliferation and differentiation of NSCs. To quickly find the ligands of bHLH factors from natural products extract, we developed the Hes I immobilized sepharose beads-HPLC method. Flavonoid glycosides (1-3) have been isolated rapidly by this method. Compounds 1 and 3 had the inhibitory activity against the Hes 1 dimer formations, and accelerated the neuron differentiation of mouse neural stem cells (MEB5). As a "natural products + diversity-oriented synthesis (DOS)" derived library, the heterocyclic-substituted chromones or flavonoids library was constructed by our efficient synthesis method and solid phase synthesis. By constructed cell-based assay, several compounds were found as moderate Hes 1 promoter inhibitors. Compound 4 actually inhibited Hes 1 mRNA expression in NSCs. Interestingly, 4 led the NSCs to astrocyte selective differentiation. We also searched upregulators of Ngn2 expression, which is bHLH differentiation activator. The cell-based assay for Ngn2 promoter activity was constructed. By Ngn2 promoter activity guided separation, several activators were isolated from Butea superba. Of them, three compounds (5-7) showed neuron selective differentiation of NSCs.

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Synthesis of Fuligocandin B derivatives and TRAIL-resistance-overcoming activity

A. Arai Midori, Uchiyama Kento, Seto Junya, Minakawa Tomohiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  37 ( 0 ) 122 - 122 2011

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During our studies on a search for natural products from myxomycetes, we have isolated novel compounds, Fuligocandin A and B containing cycloanthranilylproline skeleton, from the extract of fruit bodies of <I>Fuligo candida</I>. Fuligocandin B consists of three residues, anthranilic acid, L-proline, and indole-3-carboxyaldehyde. Enantioselective total synthesis of Fuligocandin A, B were achieved. Moreover we synthesized 11a-CH<SUB>3</SUB> derivatives of Fuligocandin A, B. Fuligocandin B and its derivatives have TRAIL-resistance-overvoming activities on the AGS cells. For construction of the Fuligocandin B chemical library to find new active compounds, solid-phase reactions were examined.

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Synthesis of rocaglamide derivatives with heterocyclic units

Arai Midori A., Yanase Natsuki, Minakawa Tomohiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  37 ( 0 ) 78 - 78 2011

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Rocaglamide derivatives, which are one of the cyclopenta[<I>b</I>]benzofuran compounds including in plants of Asian and Western Pacific region, are counted on bioactivities. We isolated two rocaglamide derivatives from leaves of <I>Amoora cucullata</I> (Meliaceae). They showed very strong activity in sensitizing to TRAIL, which leads to apoptosis of cancer cells. In this research, we aim to synthesize rocaglamide derivatives with heterocyclic units to discover their extraordinary potential. As first, we succeed the efficient synthesis of 2-furanyl-3-hydroxy-chromone. A phtochemical [3+2]-cycloaddition between the furanylchromone and methyl cinnamate smoothly proceeded. Base-induced rearrangement and reduction gave a 3a-furanyl-rocaglamide derivative in 6 steps 11% yield.

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ウィントシグナルに作用する天然物:タイおよびバングラデシュ植物のスクリーニング

ISHIBASHI MASAMI, YAMAGUCHI TATSUHIRO, MORI NAOMI, LI XIAOFAN, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, SADHU SAMIR K

香料・テルペンおよび精油化学に関する討論会講演要旨集 54th   139 - 141 2010.10

放線菌からのWntシグナル阻害作用を持つ天然物の探索

TAMAI YUMI, TOUME KAZUFUMI, ARAI MIDORI, ISHIBASHI MASAMI

日本薬学会関東支部大会講演要旨集 54th   64 2010.10

TRAILシグナルを介してがん選択的にアポトーシスを誘導する天然物の探索

TOUME KAZUFUMI, AHMED FIROJ, NAKAZAWA TAKAFUMI, OTSUKI TAKASHI, ARAI MIDORI, ISHIBASHI MASAMI

天然有機化合物討論会講演要旨集 52nd   31 - 36 2010.09

Stereochemistry of new triterpene TA1 isolated from <I>Tubulifera arachnoidea</I>

Ishii Kensuke, arai midori, Ippongi Yukihito, Ishibashi masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  36 ( 0 ) 140 - 140 2010

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TA1, a new triterpenoid acid was isolated from the myxomycete <I>Tubulifera arachnoidea</I>, and its structure was elucidated by spectral data. However, the stereochemistry of the position of 22 and 23, diol moiety of side chain, couldn't be determinated in comparison with the data of papers. Then our purpose is determination of these stereochemistry in comparison with the spectral data of the synthetic model compounds, four diasteromers with the similar side chain. Syn diol model compounds were synthesized from stigmasterol. These spectral data had a significant difference and were suitable for comparison with the data of TA1. The opening of epoxide to provide anti diol model compounds is now under way.

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The synthesis of flavonoid library with heterocycles and its application to regenerative medicine for neurons

Arai Midori A., Yanase Natsuki, Koryudzu Kazune, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  36 ( 0 ) 59 - 59 2010

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Flavonoids are important bioactive compounds. To find new bioactive chromones and flavonoids, an efficient synthesis method that can add structural or substitutional diversity to molecules is important. We developed efficient one-pot synthesis of new chromone or flavonoid derivatives bearing heterocycle units by Michal-aldol reaction. To introduce additional diversity points on the molecules, Suzuki-Miyaura and Sonogashira-Hagihara coupling were performed. We also examined these reactions in solid-phase, and finally established a diverse molecule library with the naturally occurring scaffolds chromone and flavone by split & pool synthesis. The synthesized compounds are evaluated their inhibition of Hes1 promoter activities, which is one of the transcriptional factors in neural stem cells. As the result, we achieved to establish heterocyclic flavonoid or chromone library consisted of 561 compounds. Of them, we succeeded in finding 6 inhibitors of Hes1 promoter activity.

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Approaches for Discovery of Naturally Occurring Products using Immobilized Proteins

Arai Midori, Kobatake Eiji, Masada Ayako, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  51 ( 0 ) 55 - 60 2009

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Highly efficient screening method of naturally occurring products that bind to a specific target protein was demonstrated by using hVDR-magnetic beads. The native ligand 1α,25(OH)_2VD_3 was selectively bound by hVDR magnetic beads when present in a mixture of natural compounds. Furthermore, this method was proven to be applicable to the identification of natural products, which interact with a specific protein immoblized on the beads, from an extract of a natural resource. Two new natural compounds were isolated by this method. This approach will be helpful for the discovery of novel, neturally occurring products that bind to specific target proteins. A high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1 was construcrted. Successful demerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labeled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.

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Synthesis and Evaluation of Fuligocandin A, B and their Derivatives Isolated from Fuligo candida

A. Arai Midori, Seto Junya, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  35 ( 0 ) 144 - 144 2009

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During our studies on a search for natural products from myxomycetes, we have isolated novel compounds, fuligocandin A and B containing cycloanthranilylproline skeleton, from the extract of fruit bodies of Fuligo candida. We studied the total synthesis of fuligocandin A, B and its derivatives. Fuligocandin B consists of three residues, anthranilic acid, L-proline, and indole-3-carboxyaldehyde. Total synthesis of fuligocandin A, B and their enantiomers and fuligocandin B derivatives were achieved.TRAIL-resistance overcoming activities of fuligocandin A, B and their enantiomers and fuligocandin B derivatives AGS cells were evaluated. Fuligocandin B and its derivatives showed effects on the TRAIL-resistance AGS cells.

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Synthesis and development of compounds for nervous system regeneration after spinal cord injury

A.Arai Midori, Sawada Keisuke, Kubo Takekazu, Yamashita Toshihide, Sugimoto Hachiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  35 ( 0 ) 138 - 138 2009

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We are interested in a diverse compound library based on diversity oriented synthesis and searching for useful small molecules. Blebbistatin accelerates extension of axonal growth.<BR>We planned to synthesize various Blebbistatin derivatives with plural anthranilic acid units and pyrrolidone units for improvement of chemical properties and bioactivity of Blebbistatin. Four derivatives were synthesized in solution phase.<BR> Moreover, solid-phase synthesis was examined to obtain a lot of number of derivatives. For the solid phase library synthesis, pyrrolidone unit was attached to Merrifield resin. Solid-phase arylation of amide was examined by using arylboronic acid and Cu(OAc)<SUB>2</SUB>.

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天然物を基盤とするWntおよびHedgehogシグナル阻害剤の探索

荒井緑, 石橋正己

ファルマシア 45   121 - 125 2009

2-II-21 ヒト前立腺由来PZ-HPV-7細胞におけるビタミンD_3誘導体の細胞増殖抑制作用および代謝(一般研究発表,新世紀ビタミン学の展望と先進的展開を目指して,日本ビタミン学会第60回大会発表要旨)

中林 佐知栄, 榊 利之, 鎌倉 昌樹, 池田 進之介, 荒井 緑, 橘高 敦史, 楠堂 達也, 山下 均, 太田 美穂, 生城 真一

ビタミン (公益社団法人 日本ビタミン学会)  82 ( 4 ) 275 - 275 2008

ISSN  0006-386X

28 Search the Wnt Signaling Inhibitor with Frameworks Trusted in Nature(Oral Presentation)

Arai Midori A, Hanazawa Shuwa, Uchino Yujiro, Li Xiaofan, Numata Terumi, Sugimitsu Noriko, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  50 ( 0 ) 191 - 196 2008

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Natural products have their important meanings in biological systems. Isolation of new natural products and synthesis of small molecules based on their scaffolds would be of chemical relevance to living cells and organs. In this study, we focused on the Wnt signaling, which pathways show aberrant activation in many cancer cells. We synthesized natural products melleumin A (1) and B (2), and trans-dihydroarcyriarubin C, which were isolated by us from myxomycetes (true slime molds), and also synthesized their isomers. Melleumin A (1) and B (2) are novel peptide compounds isolated from the myxomycete Physarum melleum. Their syntheses have been achieved by coupling procedures of their components, L-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid. We found cis-dihydroarcyriarubin C (12), and isomers of melleumin B are moderate inhibitors of Wnt signal transcription. We also developed a high-throughput system for analyzing of inhibition of making a complex between TCF and β-catenin by using microplates. The regulation of transcription by TCF/β-catenin complex is a final step of the Wnt signal pathway. In this assay, cis-dihydroarcyriarubin C (12) showed inhibition, which indicates that a cell-based Wnt signal inhibition would be caused by disruption of TCF/β-catenin complex. We also found several natural products from our natural products library that show a cell-based Wnt signal inhibition and a protein-based TCF/β-catenin complex inhibition.

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Library Construction Study of Chromone, Flavonoid Derivatives with Diverse Heterocyclic Units

Arai Midori.A, Sawada Keisuke, Sato Mina, Morizane Takeo, Hosoya Takahiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  34 ( 0 ) 143 - 143 2008

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We are interested in a diverse compounds library based on natural products and searching for useful small molecules. Heterocyclic-substituted chromones and flavonoids would be expected to have important bioactivity related with some disease.4'-Benzyloxy-2'-hydroxyacetophenone reacted with various pyridinecarboxaldehydes or benzaldehydes to give intermediate chalcone derivatives, which underwent intramolecular cyclization followed by aldol reaction with another aldehyde to give various heterocyclic substituted chromones or flavonoids.On solid-phase synthesis, we can achieve these reactions under similar conditions of liquid-phase.For more diversity, Suzuki-Miyaura cross coupling progressed on both aromatic units.Some of synthesized compounds showed the inhibition of GLI-mediated transcription, cytotoxicity against some cancer cells and promoted differentiation of neural stem cell.

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Synthesis and Evaluation of Melleumin Derivatives from the Myxomycete; an Approach for Wnt Signal Inhibitors Trusted in Nature

Arai Midori A, Uchino Yujiro, Hanazawa Shuwa, Li Xiaofan, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  34 ( 0 ) 61 - 61 2008

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During our studies in a search for natural products from myxomycetes, we have isolated a novel peptide lactone, melleumin A , and its seco acid methyl ester, melleumin B , from the cultured plasmodium of the myxomycete Physarum melleum. We studied the total synthesis of melleumin A, B and their diastereomers. Melleumin A and B consist of four residues, p-methoxybenzoic acid, L-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid. Total synthesis of melleumin A, B and their diastereomers were achieved by a stereoselective method. The Wnt signal inhibitory activities of melleumin A, B and their diastereomers were evaluated. The 3R-epimer, 10R-epimer and (3R, 4S, 10R, 11R)-isomer of melleumin B showed moderate inhibition of the Wnt signaling pathway.

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16 Search for Natural Products Targeting Hedgehog Signaling Pathway

Hosoya Takahiro, Arai Midori A, Tateno Chikashi, Koyano Takashi, Kowithayakom Thaworn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  49 ( 0 ) 91 - 96 2007

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The hedgehog (Hh)/GLI signaling pathway has been implicated not only in a variety of developmental processes in wide range of organisms, but also in the formation and development of different tumors including skin, brain, prostate, upper gastrointestinal tract, pancreas and lung. Targeting Hh/GLI signaling has been expected as an effective cancer therapeutic strategy. To find the specific inhibitors of Hh/GLI signaling pathway from natural resources, a cell-based screening assay system targeting transcriptional activator GLI1, which constitutes the final step in the Hh signaling pathway, was constructed. A pGL4-Luc reporter vector inserted with 12×GLI binding sites was stably transfected into HaCaT cell line expressing GLI1 under tetracycline repressor control. A suitable protocol for the screening was then established. The screening of our natural products library with the above constructed system identified six active compounds; staurosporinone (1), 6-hydroxystaurosporinone (2), arcyriaflavin C (3), 5,6-dihydroxyarcyriaflavin A (4), zerumbone (5), and zerumbone epoxide (6). Their IC_&lt;50&gt; values of GLI1 transcriptional inhibitory activity were 1.8, 3.6, 11.3, 6.9, 3.0 and 55μM, respectively. The next screening of our natural plants extracts library gave 15 hit plants. Repeated chromatography separations of the MeOH extracts of Physalis minima and Zizyphus cambodiana gave active compounds. P minima gave two compounds; physalin F (10) and physalin B (11), and Z. combodiana a compound; colubrinic acid (13). Their IC_&lt;50&gt; values were 0.66, 0.62 and 29μM, respectively. It was reported that glil, ptchl, bcl2 are the Hh/GLI-mediated transcriptional targets. The influences of these inhibitors (1, 5, 10 and 11) on these protein expressions were investigated with western blotting analysis. These inhibitors decreased the expression of GLI1 and PTCH1, which are related Hh signaling pathway. Moreover, BCL2, which is related with apoptosis, was also decreased.

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Efficient Synthesis of Chromone and Flavonoid Derivatives by Michael-aldol Reaction

Arai Midori.A, Sato Mina, Sawada Keisuke, Hosoya Takahiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  33 ( 0 ) 18 - 18 2007

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We describe the one-pot synthesis by Michael-aldol reaction of chromone and flavonoid derivatives bearing pyridine units. 4'-Benzyloxy-2'-hydroxyacetophenone (1) reacted with various pyridinecarboxaldehyde (2) to give intermediate chalcone derivatives, which underwent intramolecular cyclization followed by aldol reaction with another aldehyde. The endo 2,3-disubstituted chromones were obtained in one step as the only or major product. Furthermore, use of substituted benzaldehydes (Aldehyde A) and subsequent addition of 2 (Aldehyde B) gave 3-pyridyl-substituted flavones. Some of synthesized compounds showed the inhibition of GLI-mediated transcription, and cell growth inhibitory activity against HeLa cells.

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Synthesis study of Melleumin A and B

Hanazawa Shuwa, Arai Midori, Uchino Yujiro, Ishibashi Masami

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  33 ( 0 ) 56 - 56 2007

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A novel peptide lactone, melleumin A, and its <i>seco</i> acid methyl ester, melleumin B, were isolated from cultured plasmodium of the myxomycete <i>Physarum melleum</i>. We studied the total synthesis of melleumin A and B. Melleumin A and B consist of four residues, <i>p</i>-methoxybenzoic acid, L-threonine, glycine, and an unusual amino acid, a tyrosine-attached acetic acid. Total synthesis of melleumin B was achieved by a stereoselective method, which provided further evidence for the all absolute stereochemistry of melleumin B. The Wnt signal inhibitory actives of melleumin B and its 10-epimer were evaluated. 10-epimer of melleumin B showed moderate inhibition of Wnt signal transcription.

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2-I-21 14-epi-25-hydroxy-19-norvitamin D_3誘導体の分子設計と合成(一般研究発表,日本ビタミン学会 第58回大会研究発表要旨)

荒井 緑, 原 英己, 堤 龍司, Chen Tai C, 橘高 敦史

ビタミン (日本ビタミン学会)  80 ( 4 )  2006.04

ISSN  0006-386X

シトクロムP450による25(OH)-19-ノルおよび1α,25(OH)2-19-ノルビタミンD3の代謝(一般研究発表,日本ビタミン学会 第58回大会研究発表要旨)

漆野 奈穂子, 生城 真一, 中林 佐知栄, 鎌倉 昌樹, 荒井 緑, 堤 龍司, 橘高 敦史, 太田 美穂, 井上 國世, 榊 利之

ビタミン (日本ビタミン学会)  80 ( 4 ) 224 - 224 2006.04

ISSN  0006-386X

2-C-4 前立腺がんを標的としたプロホルモン型25(OH)-19-ノルビタミンD_3誘導体(第57回大会一般研究発表)(第57回大会研究発表要旨)

荒井 緑, 堤 龍司, Chen Tai C, Holick Michael F, 榊 利之, 漆野 奈穂子, 井上 國世, 橘高 敦史

ビタミン (日本ビタミン学会)  79 ( 4 )  2005.04

ISSN  0006-386X

Design of the Vitamin D Analogs Aiming at the Recovery of the Affinity for Mutant Vitamin D Receptor

Honzawa Shinobu, Takahashi Naoyuki, Yamashita Atsushi, Sugiura Takayuki, Kurihara Masaaki, Arai Midori A, Kato Shigeaki, Kittaka Atsushi

Proceedings of the Symposium on Progress in Organic Reactions and Syntheses (Division of Organic Chemistry, The Pharmaceutical Society of Japan)  31 ( 0 ) 80 - 80 2005

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1&amp;alpha;,25-Dihydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt;(1) has a wide range of biological activities, for example, calcium and phosphorus homeostasis, cell growth and differentiation. The actions of 1 are mediated by a specific nuclear receptor, vitamin D receptor (VDR). Hydrogen bonds between three hydroxyl groups of 1 and hydrophilic amino acids in the ligand-binding domain (LBD) of VDR are essential for its actions. Arginine 274 is known to form hydrogen bond with 1&amp;alpha;-OH of 1, and its mutation lead to loss of the affinity and its actions. For the mutant VDR we designed the analogs having a CH&lt;sub&gt;3&lt;/sub&gt; or HOCH&lt;sub&gt;2&lt;/sub&gt; group on its 1&amp;alpha;-position to effect hydrophobic interaction. A coupling reaction of CD ring bromoolefin and A ring enyne was carried out by the method developed by Trost. A ring enynes for 1&amp;alpha;-CH&lt;sub&gt;3&lt;/sub&gt; and 1&amp;alpha;-HOCH&lt;sub&gt;2&lt;/sub&gt; analogs were prepared from D-galactose and D-glucose, respectively.

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Relationship of stereochemical and skeletal diversity of small molecules to cellular measurement space

YK Kim, MA Arai, T Arai, JO Lamenzo, EF Dean, N Patterson, PA Clemons, SL Schreiber

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (AMER CHEMICAL SOC)  126 ( 45 ) 14740 - 14745 2004.11

ISSN  0002-7863

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Systematic and quantitative measurements of the roles of stereochemistry and skeleton-dependent conformational restriction were made using multidimensional screening. We first used diversity-oriented synthesis to synthesize the same number (122) of [10.4.0] bicyclic products (B) and their corresponding monocyclic precursors (M). We measured the ability of these compounds to modulate a broad swath of biology using 40 parallel cell-based assays. We analyzed the results using statistical methods that revealed illuminating relationships between stereochemistry, ring number, and assay outcomes. Conformational restriction by ring-closing metathesis increased the specificity of responses among active compounds and was the dominant factor in global activity patterns. Hierarchical clustering also revealed that stereochemistry was a second dominant factor; whereas the stereochemistry of macrocyclic appendages was a determinant for bicyclic compounds, the stereochemistry of the carbohydrates was a determinant for the monocyclic compounds of global activity patterns. These studies illustrate a quantitative method for measuring stereochemical and skeletal diversity of small molecules and their cellular consequences.

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Accelerated glycosylation under frozen conditions

M Takatani, J Nakano, MA Arai, A Ishiwata, H Ohta, Y Ito

TETRAHEDRON LETTERS (PERGAMON-ELSEVIER SCIENCE LTD)  45 ( 20 ) 3929 - 3932 2004.05

ISSN  0040-4039

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O-Glycosylations using thiomethyl glycosides as donors were compared under both frozen and unfrozen conditions. In the presence of MeOTf as a promoter, enormous rate acceleration was observed when the glycosylation was conducted in p-xylene below its freezing point. (C) 2004 Elsevier Ltd. All rights reserved.

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Development of the first spiro bis(is oxazoline)ligands (SPRIXs) and their applications to catalytic enantioselective reactions

MA Arai, T Shinohara, T Arai, H Sasai

JOURNAL OF SYNTHETIC ORGANIC CHEMISTRY JAPAN (SOC SYNTHETIC ORGANIC CHEM JPN)  62 ( 1 ) 59 - 69 2004.01

ISSN  0037-9980

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The first chiral isoxazoline ligands bearing spiro skeleton are developed. The spiro bis(isoxazoline) ligands (SPRIXs) are readily synthesized from diethyl malonate via double intramolecular nitrile oxide cycloaddition as a key step. The complex of (M, S, S)-R-SPRIX and Pd(OCOCF3)(2) promoted the catalytic asymmetric Wacker-type cyclization of alkenyl alcohols to give optically active cyclic ethers for the first time. Furthermore, starting from dialkenyl alcohol, the enantioselective tandem cyclization via oxy-palladation was achieved with up to 95% ee. Asymmetric ligands other than SPRIXs promote neither the Wacker-type reaction nor the tandem reaction.

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Spiro bis(isoxazole) as a new chiral ligand

K Wakita, MA Arai, T Kato, T Shinohara, H Sasai

HETEROCYCLES (PERGAMON-ELSEVIER SCIENCE LTD)  62   831 - 838 2004.01

ISSN  0385-5414

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A novel bis(isoxazole) ligand, (M*)-4,4',5,5',6,6',7,7'-octahydro-7,7'-spirobi[benzo[c]isoxazole] (5) bearing a spiro chirality was designed and synthesized. Characterization of the ligand and its application to the enantioselective tandem cyclizaton of alkenyl alcohol via oxy-palladation are described.

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Synthesis of fluorine substituted oligosaccharide analogues of monoglucosylated glycan chain, a proposed ligand of lectin-chaperone calreticulin and calnexin

Y Ito, S Hagihara, MA Arai, Matsuo, I, M Takatani

GLYCOCONJUGATE JOURNAL (KLUWER ACADEMIC PUBL)  21 ( 5 ) 257 - 266 2004

ISSN  0282-0080

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As a part of a exploring the N-glycan-mediated glycoprotein quality control in endoplasmic reticulum, 2-fluorinated derivative Glcalpha1 --&gt; 3Man(F) 1, Glcalpha1 --&gt; 3Man(F) alpha1 --&gt; 2Man2, and Glcalpha1 --&gt; 3Man(F) alpha1 --&gt; 2Manalpha1 --&gt; 2Man 3 were synthesized in a concise manner. These oligosaccharides were subjected to binding studies with calreticulin by using isothermal titration calorimetry. It was revealed that disaccharide 1 was a poor ligand, while tri-( 2) and tetrasaccharide ( 3) had observable affinity.

Synthesis of glycoprotein molecular probes for the analyses of protein quality control system

K Totani, Matsuo, I, M Takatani, MA Arai, S Hagihara, Y Ito

GLYCOCONJUGATE JOURNAL (KLUWER ACADEMIC PUBL)  21 ( 1-2 ) 69 - 74 2004

ISSN  0282-0080

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Synthesis of novel chiral spiro bis(pyrazole) ligands

S Takizawa, Y Honda, MA Arai, T Kato, H Sasai

HETEROCYCLES (PERGAMON-ELSEVIER SCIENCE LTD)  60 ( 11 ) 2551 - 2556 2003.11

ISSN  0385-5414

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The first synthesis of spiro bis(pyrazole) ligands, 2,2',4,4'-tetrahydro-6,6'-spirobi[5H-cycopentapyrazole] (l a) and 2,2'-dibenzyl-2,2',4,4'-tetrahydro-6,6'-spirobi[5H-cycopentapyrazole] (1b) was achieved. The application of spiro bis(pyrazole) ligand to asymmetric catalysis was also examined.

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Enantioselective synthesis of alpha-methylene-gamma-butyrolactones using chiral Pd(II)-SPRIX catalyst

C Muthiah, MA Arai, T Shinohara, T Arai, S Takizawa, H Sasai

TETRAHEDRON LETTERS (PERGAMON-ELSEVIER SCIENCE LTD)  44 ( 28 ) 5201 - 5204 2003.07

ISSN  0040-4039

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Combination of Pd(OCOCF3)(2) and (M,S,S)-iPr-SPRIX ligand promoted the intramolecular cyclization of 2-alkynoates very effectively to form alpha-methylene-gamma-butyrolactones in good yields with up to 92% ee. (C) 2003 Elsevier Science Ltd. All rights reserved.

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Synthesis and character of new bis(isoxazoline) ligands

T Shinohara, K Wakita, MA Arai, T Arai, H Sasai

HETEROCYCLES (PERGAMON-ELSEVIER SCIENCE LTD)  59 ( 2 ) 587 - 593 2003.03

ISSN  0385-5414

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Synthesis of two kinds of new bis(isoxazoline) ligand, achiral 2,2'-bis(isoxazolinyl)propane and (R)-2,2'-bis(isoxazolinyl)-1,1'-binaphthyl bearing an axial chirality is described. Both of the bis(isoxazoline) ligands accelerated the Pd(II)-catalyzed Wacker-type cyclization of alkenyl alcohol. The isoxazoline ligands were found to be essential to promote the cyclization.

Synthesis of new chiral bis(isoxazoline) ligands containing spiro[5.5]undecane skeleton

MA Arai, M Kuraishi, T Arai, H Sasai

CHIRALITY (WILEY-LISS)  15 ( 1 ) 101 - 104 2003.01

ISSN  0899-0042

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New chiral bis(isoxazoline) ligands bearing a spiro[5.5]undecane skeleton were designed and synthesized in five steps from diethyl malonate (3). These ligands showed a coordinating ability to Cu(II) as chiral ligands. A complex of (+)-(M*,S*,R*)-[5.5]-SPRDC 2b and Cu(OTf)(2) catalyzed the conjugate addition of diethylzine to 2-cyclohexenone (8) to give (S)-3-ethyl-cyclohexanone (9) in 93% yield with 54% ee. (C) 2002 Wiley-Liss, Inc.

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The first enantioselective intramolecular aminocarbonylation of alkenes promoted by Pd(II)-spiro bis(isoxazoline) catalyst

T Shinohara, MA Arai, K Wakita, T Arai, H Sasai

TETRAHEDRON LETTERS (PERGAMON-ELSEVIER SCIENCE LTD)  44 ( 4 ) 711 - 714 2003.01

ISSN  0040-4039

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The highly ligand acceleration effect of spiro bis(isoxazoline) ligand (SPRIX) on the Pd(II)-catalyzed intramolecular aminocarbonylation of alkenyl amine derivatives was realized. Furthermore, the chiral Pd(II)-SPRIX catalyst accomplished the first enantioselective intramolecular aminocarbonylation. The reaction of N-(2,2-dimethyl-pent-4-enyl)-p-toluenesulfonamide in the presence of Pd(II)-SPRIX catalyst and p-benzoquinone in methanol under a carbon monoxide atmosphere afforded [4,4-dimethyl-1-(p-toluene-sulfonyl)-pyrrolidin-2-yl]-acetic acid methyl ester in good yield with moderate enantioselectivity. (C) 2003 Elsevier Science Ltd. All rights reserved.

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Development of the first spiro bis (isoxazoline) ligands (SPRIXs)

My Favorite Organic Synthesis The Society of Synthetic Organic Chemistry, Japan Ed. pp 176-177 2002

Development of the first spiro bis (isoxazoline) ligands (SPRIXs)

Latest Frontiers of Organic Synthesis, ed. Yuichi Kobayashi, Research Signpot 49-64 2002

A new asymmetric Wacker-type cyclization and tandem cyclization promoted by Pd(II)-spiro bis(isoxazoline) catalyst

MA Arai, M Kuraishi, T Arai, H Sasai

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (AMER CHEMICAL SOC)  123 ( 12 ) 2907 - 2908 2001.03

ISSN  0002-7863

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Design and synthesis of the first spiro bis(isoxazoline) derivatives as asymmetric ligands

MA Arai, T Arai, H Sasai

ORGANIC LETTERS (AMER CHEMICAL SOC)  1 ( 11 ) 1795 - 1797 1999.12

ISSN  1523-7060

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[GRAPHICS]A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition, The optically pure SPRIX greatly accelerated the Cu(acac)(2)-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character.

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The first chiral spiro bis(isoxazoline) ligands.

MA Arai, T Arai, H Sasai

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY (AMER CHEMICAL SOC)  217   U173 - U173 1999.03

ISSN  0065-7727

Rational design, synthesis, and evaluation of a new type of PKC inhibitor

M Sodeoka, MA Arai, K Adachi, K Uotsu, M Shibasaki

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (AMER CHEMICAL SOC)  120 ( 2 ) 457 - 458 1998.01

ISSN  0002-7863

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Asymmetric Heck reaction-carbanion capture process. Catalytic asymmetric total synthesis of (-)-Delta(9(12))-capnellene

T Ohshima, K Kagechika, M Adachi, M Sodeoka, M Shibasaki

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (AMER CHEMICAL SOC)  118 ( 30 ) 7108 - 7116 1996.07

ISSN  0002-7863

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An asymmetric Heck reaction-carbanion capture process was realized for the first time, making possible the catalytic asymmetric synthesis of various functionalized bicyclo[3.3.0]octane derivatives 6 in up to 94% ee. Sodium bromide had interesting effects on this asymmetric Heck reaction-carbanion capture process, and these effects were useful for improving the enantiomeric excess. Furthermore, the catalytic asymmetric synthesis of (-)-Delta(9(12))-capnellene (7) was achieved for the first time, using 6b as a key intermediate and a radical cyclization as a key step.

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