研究テーマ
・医療への応用を志向した機能性分子の開発
・天然からの新規生理活性物質の探索及びそれらをシーズとした機能性分子の開発
キーワード
配属学生
大学院生 | 0名 |
---|---|
学部学生 | 6年次生:11名、5年次生:18名、4年次生:13名 |
所属教員
-
平野 智也
教授 / 博士(薬学)
■担当科目
基礎有機化学実習(1年)、医薬品化学1(3年)、医薬品化学2(4年)、先端分子医科学3(6年)、アドバンスト薬物治療学3(6年)、薬学総合演習(6年)、特別演習・実習(4年~6年)
創薬化学特論I, II, III(大学院)、特別演習(大学院)
■所属学会および社会活動
日本薬学会、日本化学会、日本ケミカルバイオロジー学会、日本光医学・光生物学会 -
山田 剛司
准教授 / 博士(薬学)
■担当科目
化学・化学演習(1年)、有機スペクトル学演習(2年)、生薬・天然物化学特論(大学院)、基礎有機化学実習(1年)、特別演習・実習(4年~6年)特別演習(PBL)(大学院)
■所属学会および社会活動
日本薬学会、日本生薬学会 -
安田 大輔
助教 / 博士(薬学)
■担当科目
基礎有機化学実習 (1年)
■所属学会および社会活動
日本薬学会、日本酸化ストレス学会、日本ケミカルバイオロジー学会
Chem-Stationスタッフ
研究内容
疾患診断、治療に有用な光機能性分子の開発
光を用いる手法は、生体の非侵襲的な制御、解析を可能とするため、疾患の治療、診断において広く利用されています。当研究室では、こうした手法に用いる新たな光機能性分子の開発を行っています。例えば、疾患組織近傍などの特定の環境選択的に治療薬を光放出する分子システムや、疾患診断を可能とする蛍光物質です。分子構造を論理的にデザインするだけでなく、植物などに由来する天然物を基に開発する研究も行っています。

エピジェネティクス、エピトランスクリプトームを制御、解析する分子の開発
DNA、RNA内の核酸、DNAと複合体を形成するヒストン蛋白質では、メチル化などの化学修飾反応が起こります。塩基配列の変化を伴わずに遺伝子の活性化などを制御する、こうした修飾を解析する学問領域は、エピジェネティクス、エピトランスクリプトームと呼ばれており、修飾を制御する酵素群は新たな創薬標的として注目されています。我々は、疾患治療薬となりえるこうした酵素に対する阻害剤および、生理機能を解析するための有機化学反応の開発を行っています。

高槻市淀川流域のヨシを天然物の探索対象とする研究
その成分にアルツハイマー型認知症の予防効果を見出すことを目的とし、種々のカラムクロマトグラフィー及びHPLCを用いて分離・精製を行っています。現在、活性を示す幹皮のメタノールエキスの水溶性画分について検討を行い、これまで新規物質を含む数種の化合物を単離しています。

Phragmites australis

アルツハイマー型認知症の病理学的所見でみられるtauタンパク質によるPHF形成

微生物コミュニケーションを利用した天然化合物探索の新しいアプローチ

代表的論文
2020年
- Yamada T, Kogure H, Kataoka M, Kikuchi T, Hirano T, Nehira T, Nishii T: Halosmysin A, a novel 14-membered macrodiolide isolated from the marine-algae-derived fungus Halosphaeriaceae sp. Mar. Drugs, 18, 320/1–320/9, 2020
- Kikuchi T, Akiyama K, Koike H, In Y, Yamada T, Tanaka R: Carapanins A-C: new limonoids from andiroba (Carapa guianensis) fruit oil. Org. Biomol. Chem., 18, 9268–9274, 2020
- Asano A, Minoura K, Kojima Y, Yoshii T, Yamada T, Doi M. NMR-based quantitative studies of the conformational equilibrium between their square and folded forms of ascidiacyclamide and its analogues. RSC Adv., 10, 33317–33326, 2020
- Kikuchi T, Mori M, In Y, Zhang J, Yamada T, Hirano T: leurocorols A and B: rearranged steroids from the fruiting bodies of Pleurotus cornucopiae. Org. Chem. Front., 7, 2022–2028, 2020
- Asano A, Yamada T, Doi M.Incorporation of β-amino acids into ascidiacyclamides: Effects on conformation, cytotoxicity and interaction with copper (II) ion. J. Pep. Sci., 25, e3225/1–e3225/10, 2020
- 平野智也、新たな構造・機能を持った光機能分子の開発、ファルマシア、56(12), 1112-1116, 2020
2019年
- H. Yokoo, H. Kagechika, A. Ohsaki, T. Hirano, A Polarity‐Sensitive Fluorescent Amino Acid and its Incorporation into Peptides for the Ratiometric Detection of Biomolecular Interactions, ChemPlusChem, 84, 1716-1719, 2019. (Featured in ChemistryViews Magazine, 15 December 2019, “Fluorescent Peptides Help to Detect Biomolecular Interactions”.)
- Yamada T, Tanaka R, Nehira T, Nishii T, Kikuchi T. Altercrasins A-E, decalin derivatives, from a sea-urchin-derived Alternaria sp.: isolation and structural analysis including stereochemistry. Mar. Drugs, 17, 218/1–218/10, 2019
- Inoue K, Tanaka K, Yamada T, Koshino H, Hashimoto M. Isolation of peribysins O, P, and Q from Periconia macrospinosa KT3863 and configurational reinvestigation of peribysin E diacetate from Periconia byssoides OUPS-N133. J. Nat. Pro., 82, 911–918, 2019
- Yamada T, Fujii A, Kikuchi T. New Diterpenes with a Fused 6-5-6-6 Ring System Isolated from the Marine Sponge-Derived Fungus Trichoderma harzianum. Mar. Drugs, 17, 480/1–10, 2019
- 平野智也、植物由来の天然物を基にした蛍光物質の創製、アグリバイオ、3(2), 61-65, 2019.
2018年
- Hirano T, Fujiwara T, Niwa H, Hirano M, Ohira K, Okazaki Y, Sato S, Umehara T, Maemoto Y, Ito A, Yoshida M, Kagechika H, Development of novel inhibitors for histone methyltransferase SET7/9 based on cyproheptadine. ChemMedChem, 13, 1530-1540 (2018) (Selected as “Cover Features”).
- Yokoo Y, Ohsaki A, Kagechika H, Hirano T, Unique properties of 1,5-naphthyridin-2(1H)-one derivatives as environmental-polarity-sensitive fluorescent dyes. Eur. J. Org. Chem. 679-687, 2018 (Selected as “Outstanding Organics”).
- Urushibara K, Masu H, Mori H, Azumaya I, Hirano T, Kagechika H, Tanatani A, Synthesis and Conformational Analysis of Alternately N‑Alkylated Aromatic Amide Oligomers. J. Org. Chem. 83, 14338-14349, 2018.
- Tojo Y, Urushibara K, Yamamoto S, Mori H, Masu H, Kudo M, Hirano T, Azumaya I, Kagechika H, Tanatani A, Conformational Properties of Aromatic Oligoamides Bearing Pyrrole Rings. J. Org. Chem. 83, 4606-4617, 2018.
- Sasayama A, Akita K, Ohya H, Kikuchi T, In Y, Fujitake M, Yamada T, Tanaka R: Guianofruits A and B from the fruit oil of andiroba (Carapa guianensis, Meliaceae) and their effects on LPS-activated NO Production. Chem.Select, 3:6056-6060, 2018
- Kikuchi T, Kitaura K, Katsumoto A, Zhang J, Yamada T, Tanaka R: Three bisabolane-type sesquiterpenes from edible mushroom Pleurotus eryngii. Fitoterapia, 129:108-113, 2018
- Yamada T, Matsyda M, Seki M, Hirose M, Kikuchi T: Sterepinic acids A-C, new carboxylic acids produced by a marine alga-derived fungus. Molecules, 23:1336/1-1336/10, 2108
- Inoue T, Ohmori S, Ohya H, Kikuchi T, Yamada T, Tanaka R: Carapanosins D-F from the seeds of andiroba (Carapa guianensis, Meliaceae) and their effects on LPS-activated NO production. Molecules, 23:1778/1-1778/9, 2108
- Zhang J, Zhu W-F, Zhu W-Y, Yang P-P, Xu J, Manosroi J, Kikuchi T, Abe M, Akihisa T, Feng F: Melanogenesis-inhibitory and cytotoxic activities of chemical constituents from the leaves of Sauropus androgynus L. MERR. (Euphorbiaceae). Chem. Biodivers., 15: e1700486, 2018
- Zhang J, Akihisa T, Kurita M, Kikuchi T, Zhu W-F, Ye F, Dong Z-H, Liu W-Y, Feng F, Xu J: Melanogenesis-inhibitory and cytotoxic activities of triterpene glycoside constituents from the bark of Albizia procera. J. Nat. Prod., 81: 2612-2620, 2018
- Miao D., Zhang T-Q, Xu J, Ma C-Y, Liu, W-Y, Kikuchi T, Akihisa T, Abe M, Feng F, Zhang J: Three new cardiac glycosides obtained from the roots of Streblus asper Lour. and their cytotoxic and melanogenesis-inhibitory activities. RSC Adv., 8: 19570-19579, 2018
- Morikawa T, Nagatomo A, Kitagawa K, Muraoka O, Kikuchi T, Yamada T, Tanaka R, Ninomiya K: Collagen synthesis-promoting effects of andiroba oil and its limonoid constituents in normal human dermal fibroblasts. J. Oleo Sci., 67: 1271-1277, 2018
- Yamada T, Kajimoto J, Kikuchi T, Tanaka R: Elucidation of the relationship between CD Cotton effects and the absolute configuration of sixteen stereoisomers of spiroheterocyclic-lactams. Mar. Drugs 16: 223/1–223/12, 2018
- Hirano T, Mori S, Kagechika H, Development of functional molecules for regulating and elucidating histone methyltransferase. Chemical Record, 18, 1745-1759, 2018.
2017年
- Mori S, Hirano T, Takaguchi A, Fujiwara T, Okazaki Y, Kagechika H, Selective reagent for detection of N-ε-monomethylation of peptide lysine residue via SNAr reaction. Eur. J. Org. Chem. 3606-3611, 2017.
- Endo Y, Kasahara T, Harada K, Kubo M, Etoh T, Ishibashi M, Ishiyama A, Iwatsuki M, Otoguro K, Omura S, Akisue G, Hirano T, Kagechika H, Fukuyama Y, Ohsaki A, Sucupiranins A−L, Furanocassane Diterpenoids from the Seeds of Bowdichia virgilioides. J. Nat. Prod. 80, 3120−3127, 2017.
- Yamada T, Suzue M, Arai T, Kikuchi T, Tanaka R: Trichodermanins C–E, new diterpenes with a fused 6-5-6-6 ring system produced by a marine sponge-derived fungus. Mar. Drugs, 15:169/1-169/7, 2017
- Yamada T, Kimura H, Arimitsu T, Kajimoto T, Kikuchi T, Tanaka R: Absolute configuration of eight cephalimysins isolated from the marine-derived Aspergillus fumigatus. ChemistrySelect, 2: 10936 -10940, 2017
- Asano A, Numata S, Yamada T, Minoura K, Doi M: Conformational properties of ascydiacyclamide analogues with cyclic α-amino acids instead of oxazoline residues. Bioorg. Med. Chem., 25: 6554-6562, 2017
- Higuchi K, Tani Y, Kikuchi T, In Y, Yamada T, Muraoka O, Tanaka N, Tanaka R: Guianolactones A and B, two rearranged pentacyclic limonoids from the seeds of Carapa guianensis. Chem.-Asian J., 12: 3000-3004, 2017
- Kikuchi T, Horii Y, Maekawa Y, Masumoto Y, In Y, Tomoo K, Sato H, Yamano A, Yamada T, Tanaka R: Pleurocins A and B: unusual 11(9→7)-abeo-ergostanes and eringiacetal B: A 13,14-seco-13,14-epoxyergostane from fruiting bodies of Pleurotus eryngii and their inhibitory effects on nitric oxide production. J. Org. Chem., 82: 10611-10616, 2017
- Kikuchi T, Ueno Y, Hamada Y, Furukawa C, Fujimoto T, Yamada T, Tanaka R: Five new limonoids from peels of satsuma orange (Citrus reticulata). Molecules, 22: 907/1-907/10, 2017
- Higuchi K, Miyake T, Ohmori S, Tani Y, Minoura K, Kikuchi T, Yamada T, Tanaka R: Carapanosins A-C from seeds of andiroba (Carapa guianensis, Meliaceae) and their effects on LPS-activated NO production. Molecules, 22: 502/1-502/9, 2017
- Kikuchi T, Motoyashiki N, Yamada T, Shibatani K, Ninomiya K, Morikawa T, Tanaka R: Ergostane-type sterols from king trumpet mushroom (Pleurotus eryngii) and their inhibitory effects on aromatase. Int. J. Mol. Sci., 18: 2479/1-2479/10, 2017
- 平野智也、森修一、影近弘之「ヒストンメチル化酵素を標的とする創薬およびケミカルバイオロジー研究」MedChemNews, 27(4), 208-212, 2017.
2016年
- Hirano T, Noji Y, Shiraishi T, Ishigami-Yuasa M, Kagechika H, Development of an ‘OFF-ON-OFF’ fluorescent pH sensor suitable for the study of intracellular pH. Tetrahedron 72, 4925-4930, 2016.
- Yokoo H, Ohsaki A, Kagechika H, Hirano T, Structural development of canthin-5,6-dione moiety as a fluorescent dye and its application to novel fluorescent sensors. Tetrahedron 72, 5872-5879, 2016.
- Fujiwara T, Ohira K, Urushibara K, Ito A, Yoshida M, Kanai M, Tanatani A, Kagechika H, Hirano T, Steric structure-activity relationship of cyproheptadine derivatives as inhibitors of histone methyltransferase SET7/9. Bioorg. Med. Chem. 24, 4318-4323, 2016.
- Takemoto Y, Ito A, Niwa H, Okamura M, Fujiwara T, Hirano T, Handa N, Umehara T, Sonoda T, Ogawa K, Tariq M, Nishino N, Dan S, Kagechika H, Yamori T, Yokoyama S, Yoshida M, Identification of cyproheptadine as an inhibitor of SET domain containing lysine methyltransferase 7/9 (Set7/9) that regulates estrogen-dependent transcription, J. Med. Chem. 59, 3650-3660, 2016.
- Kinoshita M, Negishi M, Sakai H, Hirano T, Mori S, Fujii S, Kagechika H, Tanatani A, Development of 6-Arylcoumarins as Nonsteroidal Progesterone Antagonists. Structure-activity Relationships and Fluorescence Properties. Bioorg. Med. Chem. 24, 5602-5610, 2016.
- Yamada T, Ohshima M, Yuasa K, Kikuchi T, Tanaka R: Assignment of the CD cotton effect to the chiral center in pseurotins, and the stereochemical revision of pseurotin A2. Mar. Drugs, 14:e74, 2016
- Suzue M, Kikuchi T, Tanaka R, Yamada T: Tandyukisins E and F, novel cytotoxic decalin derivatives isolated from a marine sponge-derived fungus. Tetrahedron Lett., 57:5070-5073, 2016
- Ninomiya K, Miyazawa S, Ozeki K, Matsuo N, Muraoka O, Kikuchi T, Yamada T, Tanaka R, Morikawa T: Hepatoprotective limonoids from andiroba (Carapa guianensis). Int. J. Mol. Sci., 17:e591, 2016
- Kikuchi T, Tanaka A, Uriuda M, Yamada T, Tanaka R: Three Novel Triterpenoids from Taraxacum officinale roots. Molecules, 21:e1121, 2016
- Kikuchi T, Maekawa Y, Tomio A, Masumoto Y, Yamamoto T, In Y, Yamada T, Tanaka R: Six new ergostane-type steroids from king trumpet mushroom (Pleurotus eryngii) and their inhibitory effects on nitric oxide production. Steroids, 115:9-17, 2016
- Asano A, Minoura K, Yamada T, Doi M: Conformational transformation of ascidiacyclamide analogs induced by incorporating enantiomers of phenylalanine, 1-naphthylalanine or 2-naphthylalanine. J. Pept. Sci., 22:156-165, 2016
- Baba S., Ueno Y., Kikuchi T., Tanaka R., Fujimori K.: A Limonoid kihadanin B from immature Citrus unshiu peels suppresses adipogenesis through repression of the Akt-FOXO1-PPARγ axis in adipocytes. J. Agric. Food Chem., 64:9607-9615, 2016
2015年
- Shiraishi T, Kagechika H, Hirano T, 6-Arylcoumarins: versatile scaffolds for fluorescent sensors, New. J. Chem. 39, 8389-8396, 2015.
- Inoue K, Urushibara K, Kanai M, Yura K, Fujii S, Ishigami-Yuasa M, Hashimoto Y, Mori S, Kawachi E, Matsumura M, Hirano T, Kagechika H, Tanatani A, Design and synthesis of 4-benzyl-1-(2H)-phthalazinone derivatives as novel androgen receptor antagonists. Eur. J. Med. Chem. 102, 310-319, 2015.
- Yamada T, Umebayashi Y, Kawashima M, Sugiura Y, Kikuchi T, Tanaka R: Determination of the chemical structures of tandyukisins B-D, isolated from a marine sponge-derived fungus. Mar. Drugs, 13:3231-3240, 2015
- Yamada T, Kikuchi T, Tanaka R: Altercrasin A, a novel decalin derivative with spirotetramic acid, produced by a sea urchin-derived Alternaria sp. Tetrahedron Lett., 56:1229-1232, 2015
- Sakamoto A, Tanaka Y, Yamada T, Kikuchi T, Muraoka O, Ninomiya K, Morikawa T, Tanaka R: Andirolides W-Y from the flower oil of andiroba (Carapa guianensis, Meliaceae). Fitoterapia, 100:81-87, 2015
- Miyake T, Ishimoto S, Ishimatsu N, Higuchi K, Minoura K, Kikuchi T, Yamada T, Muraoka O, Tanaka R: Carapanolides T-X from Carapa guianensis (andiroba) seeds. Molecules, 20:20955-20966, 2015
- Kikuchi T, Masumoto Y, In Y, Tomoo K, Yamada T, Tanaka R: Eringiacetal A, 5,6-seco-(5S,6R,7R,9S)-5,6:5,7:6,9-triepoxyergosta-8(14),22-diene-3β,7β-diol, an unusual ergostane sterol from the fruiting bodies of Pleurotus eryngii. Eur. J. Org. Chem., 2015:4645-4649, 2015
- Kikuchi T, Ikedaya A, Toda A, Ikushima K, Yamakawa T, Okada R, Yamada T, Tanaka R: Pyrazole alkaloids from watermelon (Citrullus lanatus) seeds. Phytochem. Lett., 12:94-97, 2015
- Kikuchi T, Ando H, Maekawa K, Arie H, Yamada T, Tanaka R: Two new ent-kaurane-type diterpene glycosides from zucchini (Cucurbita pepo L.) seeds. Fitoterapia, 107:69-76, 2015
- Inoue T, Matsui Y, Kikuchi T, Yamada T, In Y, Muraoka O, Sakai C, Ninomiya K, Morikawa T, Tanaka R: Carapanolides M-S from seeds of andiroba (Carapa guianensis, Meliaceae) and triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Tetrahedron, 71:2753-2760, 2015
- 山田剛司(分担執筆)
核磁気共鳴スペクトル測定法
“よくわかる薬学機器分析” 廣川書店 (2015)
2014年
- Shiraishi T, Saito T, Kagechika H, Hirano T, Development of a Novel Fluorescent Sensor to Detect a Specific Range of pH. Tetrahedron Lett., 55, 6784-6786, 2014.
- Fujii S, Sekine R, Kano A, Masuno A, Songkram C, Kawachi E, Hirano T, Tanatani A, Kagechika H, Structural development of p-carborane-based potent non-secosteroidal vitamin D analogs. Bioorg Med Chem. 22, 5891-901, 2014.
- Fujii S, Kano A, Masuno H, Songkram C, Kawachi E, Hirano T, Tanatani A, Kagechika H, Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs. Bioorg. Med. Chem. Lett., 24, 4515-4519, 2014.
- Fujii S, Kano A, Songkram C, Masuno H, Taoda Y, Kawachi E, Hirano T, Tanatani A, Kagechika H, Synthesis and structure-activity relationship of p-carborane-based non-secosteroidal vitamin D analogs. Bioorg. Med. Chem., 22, 1227-1235, 2014.
- Yamada T, Mizutani Y, Umebayashi Y, Inno N, Kawashima M, Kikuchi T, Tanaka R: Tandyukisin, a novel ketoaldehyde decalin derivative, produced by a marine sponge-derived Trichoderma harzianum. Tetrahedron Lett., 55:662-664, 2014
- Matsui Y, Kikuchi T, Inoue T, Muraoka O, Yamada T, Tanaka R: Carapanolides J-L from the seeds of Carapa guianensis (andiroba) and their effects on LPS-activated NO production. Molecules, 19:17130-17140, 2014
- Kikuchi T, Ueda S, Kanazawa J, Naoe H, Yamada T, Tanaka R: Three new triterpene esters from pumpkin (Cucurbita maxima) seeds. Molecules, 19:4802-4813, 2014
- Inoue T, Matsui Y, Kikuchi T, In Y, Muraoka O, Yamada T, Tanaka R: Carapanolides C-I from the seeds of andiroba (Carapa guianensis, Meliaceae). Fitoterapia, 96:56-64, 2014
- Asano A, Yamada T, Doi M: Modulating the structure of phenylalanine-incorporated ascidiacyclamide through fluorination. J. Pept. Sci., 20:794-802, 2014
- Kikuchi T, Ishii K, Ogihara E, Zhang J, Ukiya M, Tokuda H., Iida T, Tanaka R, Akihisa T Cytotoxic and apoptosis-inducing activities, and anti-tumor-promoting effects of cyanogenated and oxygenated triterpenes. Chem. Biodivers. 11:491-504, 2014
- 藤井晋也, 棚谷綾, 平野智也, 影近弘之「球状疎水性ファーマコフォアを有する非セコステロイド型VDR リガンドの創製研究」Vitamins (Japan), 88, 389-395, 2014