総説・解説等 - 荒井　緑

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

皆川朋皓, 當銘一文, 荒井緑, SADHU Samir, AHMED Firoj, 石橋正己

日本生薬学会年会講演要旨集 58th   139 2011年09月

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

神谷謙太朗, 森直美, 當銘一文, 荒井緑, SADHU Samir K, AHMED Firoj, 石橋正己

日本生薬学会年会講演要旨集 58th   138 2011年09月

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

玉井佑弥, 當銘一文, 荒井緑, 石橋正己

日本生薬学会年会講演要旨集 58th   215 2011年09月

ISSN  0919-1992

ウィントシグナルを制御する天然物の探索

當銘一文, 荒井緑, 石橋正己

日本生薬学会年会講演要旨集 58th   39 - 40 2011年09月

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

當銘一文, KURNIA Dikdik, HOQUE Tahmina, SADHU Samir K, AHMED Firoj, 荒井緑, 石橋正己

日本薬学会年会要旨集 131st （ 2 ） 250 2011年03月

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

皆川朋皓, 當銘一文, AHMED Firoj, SADHU Samir, 荒井緑, 石橋正己

日本薬学会年会要旨集 131st （ 2 ） 84 2011年03月

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, 中澤孝文, 當銘一文, 荒井緑, 小谷野喬, THAWORN Kowithayakorn, 石橋正己

日本薬学会年会要旨集 131st （ 2 ） 250 2011年03月

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

神谷謙太朗, 森直美, 當銘一文, 荒井緑, SADHU Samir K, AHMED Firoj, 石橋正己

日本薬学会年会要旨集 131st （ 2 ） 84 2011年03月

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

玉井佑弥, 當銘一文, 荒井緑, 石橋正己

日本薬学会年会要旨集 131st （ 2 ） 85 2011年03月

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年

ISSN  0006-386X

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P-25 神経幹細胞分化を活性化する天然物様化合物の探索(ポスター発表の部)

荒井 緑, 小柳津 和音, 柳瀬 なつき, 石川 直樹, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

天然有機化合物討論会講演要旨集 （天然有機化合物討論会実行委員会）  53 （ 0 ） 343 - 348 2011年

　概要を見る

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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ヘテロ環を有するrocaglamide類の合成研究

荒井 緑, 柳瀬 なつき, 皆川 朋晧, 石橋 正己

反応と合成の進歩シンポジウム 発表要旨概要 （日本薬学会化学系薬学部会）  37 （ 0 ） 78 - 78 2011年

　概要を見る

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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TRAIL 耐性克服を目指した変形菌由来天然物Fuligocandin B 誘導体の合成研究

荒井 緑, 内山 健人, 瀬戸 淳也, 皆川 朋皓, 石橋 正己

反応と合成の進歩シンポジウム 発表要旨概要 （日本薬学会化学系薬学部会）  37 （ 0 ） 122 - 122 2011年

　概要を見る

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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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

石橋正己, 山口達弘, 森直美, LI Xiaofan, 當銘一文, 荒井緑, 小谷野喬, 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年10月

放線菌からのWntシグナル阻害作用を持つ天然物の探索

玉井佑弥, 當銘一文, 荒井緑, 石橋正己

日本薬学会関東支部大会講演要旨集 54th   64 2010年10月

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

當銘一文, AHMED Firoj, 中澤孝文, 大槻崇, 荒井緑, 石橋正己

天然有機化合物討論会講演要旨集 52nd   31 - 36 2010年09月

変形菌<I>Tubulifera arachnoidea</I>由来新規トリテルペン TA1 の立体化学の決定

石井 健祐, 荒井 緑, 一本木 之人, 石橋 正己

反応と合成の進歩シンポジウム 発表要旨概要 （日本薬学会化学系薬学部会）  36 （ 0 ） 140 - 140 2010年

　概要を見る

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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神経再生医薬を目指した「フラボノイド+ヘテロ環」ライブラリーの構築

荒井 緑, 柳瀬 なつき, 小柳津 和音, 石橋 正己

反応と合成の進歩シンポジウム 発表要旨概要 （日本薬学会化学系薬学部会）  36 （ 0 ） 59 - 59 2010年

　概要を見る

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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10 標的タンパク質相互作用を指標とした天然物探索(口頭発表の部)

荒井 緑, 小畠 英史, 正田 亜矢子, 石橋 正己

天然有機化合物討論会講演要旨集 （天然有機化合物討論会実行委員会）  51 （ 0 ） 55 - 60 2009年

　概要を見る

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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Fuligocandin A, Bの合成と癌細胞のTRAIL耐性克服を目指した誘導体の合成

荒井 緑, 瀬戸 淳也, 石橋 正己

反応と合成の進歩シンポジウム 発表要旨概要 （日本薬学会化学系薬学部会）  35 （ 0 ） 144 - 144 2009年

　概要を見る

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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