Reviews, Commentaries, etc. - Arai, Midori

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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