基礎薬学講座　医薬化学部門

講座・部門紹介

薬品製造化学教室は1968年4月に開設され、初代荒川基一教授の元で主に単環性の複素環化合物の研究を行っていました。第二代宮坂貞教授は多環性複素環化合物の合成および生物活性の探索へと研究を展開させ、肺がんや大腸がんの治療薬であるイリノテカンの開発に成功しました。本研究室は核酸化学の分野でも研究を積極的に展開しており、第三代田中博道教授は新規ヌクレオシド誘導体の合成や新しい合成法の開発研究で多くの成果を上げられました。
2013年4月、福原が教授に着任後は、これまでの研究テーマに加えて、新たに酸化ストレスが関連する疾病を対象とした創薬研究を立ち上げました。近年、動脈硬化やアルツハイマー病、がんなど、多くの生活習慣病の発症と進行に酸化ストレスが関与していることが明らかとなってきました。そこで酸化ストレスを抑制し、生体の酸化還元（RedOx）バランスを制御することができれば、これらの病気の予防と治療が可能になると考え、以下の研究テーマに取り組んでいます。
※2021年4月より薬品製造化学部門と薬化学部門が統合し、医薬化学部門となりました。

天然抗酸化物質をファーマコフォアとした創薬

90%の病気及び老化の原因が、活性酸素による酸化ストレスが関与していることが知られています。この作用を抑制する化合物として抗酸化物質が挙げられます。これらはサプリメントとして使用されていますが、医薬品としていまだ実用化されていません。そこで天然抗酸化物質を化学修飾することで、抗酸化作用の増及び新規生理活性の発現を目指し、創薬に取り組んでいます。また、酸化ストレスの発症機構を詳細に検討して新たな創薬標的を見出し、そこに選択的に作用する治療薬や診断薬の開発も行っています。
　＊アミロイドβを創薬標的としたアルツハイマー病治療薬の開発
　＊LOX-1を創薬標的とした動脈硬化治療薬の開発
　＊RedOx制御を利用した抗がん剤の開発
　＊フェノール性抗酸化物質の生体影響の解明
　＊アルツハイマー病におけるPET診断薬の開発

新規生理活性人工核酸の開発

新規生理活性人工核酸の開発
　天然に存在するヌクレオシド(核酸)は、DNA及びRNAの構成成分として知られています。これらの構造を化学修飾したものが、エイズや肝炎などの治療薬(抗ウイルス薬)として臨床で使用されています。しかし、これらの医薬品は細胞毒性や耐性株の問題点があります。そこで既存の構造をもとに強力かつ低毒性な人工ヌクレオシドを開発するために、構造設計し合成に取り組んでいます。
　＊低細胞毒性B型肝炎治療薬の開発
　＊SAHase阻害に基づく抗マラリア薬の開発

講座員

教員（専任）

役職氏名name
教授福原 潔Fukuhara Kiyoshi
准教授太田 公規Ota Kiminori
講師森田 將夫Morita Masao
助教
清水 稚菜Shimizu Wakana

研究業績

すべて開く　＋

2025年業績

原著

Ito H, Shoji Y, Itabashi Y, Matsumoto K, Ohkubo K, Fukuhara K, Nakanishi I
Enhanced cytotoxicity against cancer cells by acetylation of a planar catechin analog
Free Radi. Res., 1-8, 2025, DOI: 10.1080/10715762.2025.2525185.

2024年業績

原著

Shimizu W, Shoji Y, Ohkubo K, Itoh H, Nakanishi I, Fukuhara K
Antioxidant activity of planar catechin conjugated with Trolox
Antioxidants, 13, 1165, 2024, DOI:doi: org/10.3390/antiox13101165

Ito H, Shoji Y, Matsumoto K, Fukuhara K, Nakanishi I
Effects of a Planar Catechin Analog on Cancer Cells
Molecules, 29, 4467, 2024, DOI:doi: 10.3390/molecules29184467

Ohinata H, Phimarn W, Mizuno M, Obama T, Fukuhara K, Makiyama T, Watanabe Y, Itabe H
Suppressive effect of resveratrol, catechin and their conformationally constrained analogs on neutrophil extracellular trap formation by HL-60-derived neutrophils
J Clin Biochem Nutr, 75, 17 - 23, DOI: 10.3164/jcbn.23-80

Ito H, Shoji Y, Matsumoto K, Fukuhara K, Nakanish I
Enhanced inhibition of cancer cell migration by a planar catechin analog
ACS Med. Chem. Lett., 15, 310 - 313, 2024, DOI:doi: 10.1021/acsmedchemlett.3c00499

2023年業績

原著

Ito H, Shoji Y, Matsumoto K, Fukuhara K, Nakanishi I
Anti-cancer effect of a planar catechin analog through the decrease in mitochondrial membrane potential
ACS Med. Chem. Lett., 14, 1478 - 1481, 2023, DOI:doi: 10.1021/acsmedchemlett.3c00328

Fujita M, Tsuchiya K, Kurohara T, Fukuhara K, Misawa T, Demizu Y
In silico optimization of peptides that inhibit Wnt/β-catenin signaling
Bioorg. Med. Chem., 84, 117264, 2023, DOI:doi: 10.1016/j.bmc.2023.117264

Fukuhara K, Nakanishi I, Imai K, Mizuno M, Matsumoto K, Ohno A
DTPA-bound planar catechin with potent antioxidant activity triggered by Fe3+ coordination
Antioxidants, 12, 225, 2023, DOI:doi: 10.3390/antiox12020225

2022年業績

原著

Tsuchiya K, Kiyoshi M, Hashii N, Fujita M, Kurohara T, Ishii-Watabe A, Fukuhara K, Misawa T, Demizu Y
Development of a penetratin-conjugated stapled peptide that inhibits Wnt/β-catenin signaling
Bioorg. Med. Chem.,73, 117021, 2022, DOI:doi: 10.1016/j.bmc.2022.117021

Mizuno M, Fukuhara K
Antioxidant and Prooxidant Effects of Thymoquinone and Its Hydroquinone Metabolite
Pharm. Bull., 45, 1389 - 1393, 2022, DOI:doi: 10.1248/bpb.b22-00199

Kanemitsu T, Ozasa E, Murase Y, Sakaue S, Miyazaki M, Nagata K, Itoh T
Asymmetric Construction of All-Carbon Quaternary Stereocenters via Organocatalytic α-Hydroxymethylation of Malonic Diesters Using Aqueous Formaldehyde
Asian Journal of Organic Chemistry, 11, 2022

Tsuchiya K, Kurohara T, Fukuhara K, Misawa T, Demizu Y
Helical Foldamers and Stapled Peptides as New Modalities in Drug Discovery: Modulators of Protein-Protein Interactions
Processes, 10, 924, 2022, DOI:doi.org/10.3390/pr10050924

Nakanishi I, Shoji Y, Ohkubo K, Ueno M, Shimoda K, Matsumoto K, Fukuhara K, Hamada H
Effect of Magnesium Ion on the Radical-Scavenging Rate of Pterostilbene in an Aprotic Medium: Mechanistic Insight into the Antioxidative Reaction of Pterostilbene
Antioxidants, 11, 340, 2022, DOI:doi: 10.3390/antiox11020340

福原　潔, 水野　美麗
天然抗酸化物質をファーマコフォアとした生活習慣病予防・治療薬の開発
昭和学士会雑誌, 81, 402 - 413, 2022

2021年業績

原著

Nakanishi I, Shoji Y, Ohkubo K, Fukuhara K, Ozawa T, Matsumoto K, Fukuzumi S
Effects of reaction environments on radical-scavenging mechanisms of ascorbic acid
J Clin Biochem Nutr, 68, 116 - 122, 2021

Nagata K, Nakagawa C, Yokoyama W, Usui H, Mochizuki R, Kanemitsu T, ;Miyazaki M, Itoh T
Synthesis and Catalytic Activities of 3-Decyl-β-proline for Michael Reactions in Water without an Organic Solvent
ACS Omege, 6, 19642 - 19646, 2021

2020年業績

原著

Kato K, Nakayoshi T, Inoue H, Fukuyoshi S, Ohta K, Endo Y, Kurimoto E, Oda A
Development of Force Field Parameters for p-Carborane to Investigate the Structural Influence of Carborane Derivatives on Drug Targets by Complex Formation
Biol Pharm Bull, 43, 1931 - 1939, 2020

Sawada N, Obama T, Mizuno M, Fukuhara K, Iwamoto S, Aiuchi T, Makiyama T, Itabe H
Transfer and enzyme-mediated metabolism of oxidized phosphatidylcholine and lysophosphatidylcholine between low- and high-density lipoproteins
Antioxidants (Basel), 9, 1045, 2020

Sakuma W, Nakagawasai O, Nemoto W, Odaira T, Ogawa T, Ohta K, Endo Y, Tan-no K
Antidepressant effect of BE360, a new selective estrogen receptor modulator, activated via CREB/BDNF, Bcl-2 signaling pathways in ovariectomized mice
Behav Brain Res, 393, 112764, 2020

Mizuno M, Mori K, Tsuchiya K, Takaki T, Misawa T. Demizu Y, Shibanuma M, Fukuhara K
Design, Synthesis, and Biological Activity of Conformationally Restricted Analogues of Silibinin
ACS Omega, 5, 23164 - 23174, 2020

Nakanishi I, Ohkubo K, Shoji Y, Fujitaka Y, Shimoda K, Matsumoto K, Fukuhara K, Hamada H
Relationship between the radical-scavenging activity of selected flavonols and thermodynamic parameters calculated by density functional theory
Free Radic Res, 54, 535 - 539, 2020

Tsuchiya K, Umeno T, Tsuji G, Yokoo H, Tanaka M, Fukuhara K, Demizu Y, Misawa T
Development of photoswitchable estrogen receptor ligands
Chem Pharm Bull (Tokyo), 68, 398 - 402, 2020

2019年業績

原著

Ohta K, Kaise A, Taguchi F, Aoto S, Ogawa T, Endo Y
Design and Synthesis of Novel Breast Cancer Therapeutic Drug Candidates Based upon the Hydrophobic Feedback Approach of Antiestrogens
Molecules, 24, 3966, 2019

Mizuno M, Mori K, Misawa T, Takaki T, Demizu Y, Shinanuma M, Fukuhara K
Inhibition of β-amyloid–induced neurotoxicity by planar analogues of procyanidin B3
Bioorg Med Chem Lett,29, 2659 - 2663, 2019

Ohta K, Ogawa T, Kato K, Oda A, Endo Y
ER subtype selectivity of m-carborane-containing phenols: C-alkyl groups on the m-carborane cage enhance ERα selectivity
Bioorg Med Chem Lett, 29, 2290 - 2293, 2019

Imai K, Nakanishi I, Ohkubo K, Ohno A, Mizuno M, Fukuzumi S, Matsumoto K, Fukuhara K
Synthesis and radical-scavenging activity of C-methylated fisetin analogues
Bioorg Med Chem, 27, 1720 - 1727, 2019

Kaise A, Endo Y, Ohta K
Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition
Bioorg Med Chem, 27, 1139 - 1144, 2019

Nakano E, Kamei D, Murase R, Taki I, Karasawa K, Fukuhara K, Iwai S
Anti-inflammatory effects of new catechin derivatives in a hapten-induced mouse contact dermatitis model
Eur J Pharmacol, 845, 40 - 47, 2019

Sasaki R, Tainaka R, Ando Y, Hashi Y, Deepak H V, Suga Y, Murai Y, Anetai M, Monde K, Ohta K, Ito I, KikuchiI H, Oshima Y, Endo Y, Nakao H, Sakono M, Uwai K, Tokuraku K
An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes
Sci Rep, 9, 2587, 2019

2018年業績

原著

Sekine E, Nakanishi I, Imai K, Ueno M, Shimokawa T, Matsumoto K, Fukuhara K
Efficient protective activity of a planar catechin analogue against radiation-induced apoptosis in rat thymocytes
RSC Advances, 8, 10158 - 10162, 2018

Kaise A, Ohta K, Fujii S, Oda A, Goto T, Endo Y
Novel androgen receptor full antagonists: Design, synthesis, and a docking study of glycerol and aminoglycerol derivatives that contain p-carborane cages
Bioorg Med Chem, 26, 3805 - 3811, 2018

2017年業績

原著

Mizuno M Nakanishi I, Matsumoto K, Fukuhara K
Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a dimer of planar catechin
Bioorg. Med. Chem. Lett. 27, 5010-5013, 2017

Kumamoto H, Fukano M, Imoto S, Kohgo S, Odanaka Y, Amano M, Kuwata-Higashi N, Mitsuya H, Haraguchi K, Fukuhara K
A novel entecavir analogue constructing with a spiro[2,4]heptane core structure in the ablycon moiety: its synthesis and evaluation for antihepatitis B virus activity
Nusleosides Nucleotides Nucleic Acid, 36, 463-473, 2017

Fukuhara K, Ohno A, Hanajiri R
A metabolic study on the biochemical effects of chiral illegal drugs in rats using 1H-NMR spectroscopy
Yakugaku Zasshi, 137, 1147-1154, 2017

Imai K, Nakanishi I, Ohkuho K, Ohba Y, Arai T, Mizuno M, Fukuzumi S, Matsumoto K, Fukuhara K
Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity
RSC Adv., 7, 17968-17979, 2017

Mizuno M, Nakanishi I, Matsubayashi S, Imai K, Arai T, Matsumoto K, Fukuhara K,
Synthesis and antioxidant activity of a procyanidin B3 analogue
Bioorg. Med. Chem. Lett. 27, 1041-1044, 2017

2016年業績

原著

1. Arai T, Ohno A, Mori K, Kuwata H, Mizuno M, Imai K, Hara S, Shibanuma M, Kurihara M, Miyata N, Nakagawa H, Fukuhara K,
Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-s C-terminal peptides,
Bioorg. Med. Chem. Lett. 26, 5468-5471, 2016

2. Arai T, Ohno A, Mori K, Kakizawa T, Kuwata H, Ozawa T, Shibanuma M, Hara S, Ishida S, Kurihara M, Miyata N, Nakagawa H, Fukuahra K,
Design, synthesis and evaluation of Trolox-conjugated amyloid- s C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer’s disease,
Bioorg. Med. Chem., 24, 4138-4143, 2016

3. Kumamoto H, Fukano M, Nakano T, Iwagami K, Takeyama C, Kohgo S, Imoto S, Amano M, Kuwata-Higashi N, Aoki M, Abe H, Mitsuya H, Fukuhara K, Haraguchi K,,
Diastereoselective synthesis of 6’’-(Z)- and 6’’-(E)-fluoro analogues of anti-hepatitis B virus agent Entecavir and its evaluation of the activity and toxicity profile of the diastereomers,
J. Org. Chem., 81, 2827-2836, 2016

4. Kaizaki-Mitsumoto A, Noguchi N, Yamaguchi S, Odanaka Y, Matsubayashi S, Kumamoto H, Fukuhara K, Funada M, Wada K, Numazawa S,
Three 25-NBOMe-type drugs, three other phenethylamine-type drugs(25I-NBMD, RH34, and escaline), eight cathinone derivatives, and a phencyclidine analog MMXE, newly identified in ingredients of drug products before they were sold on the drug market,
Forensic Toxicol., 34, 108-114, 2016.

2015年業績

原著

1. Nakanishi I, Ohkubo K, Imai K, Kamibayashi M, Yoshihashi Y, Matsumoto K, Fukuhara K, Terada K, Itoh S, Ozawa T, Fukuzumi S,
Solubilisation of a 2,2-diphenyl-1-picrylhydrazyl radical in water by s-cyclodextrin to evaluate the radical scavenging activity of antioxidants in aqueous media,
Chem. Comm., 51, 8311-8314, 2015.

2. Ieda N, Hishikawa K, Eto K, Kitamura K, Kawaguchi M, Suzuki T, Fukuhara K, Miyata N, Furuta T, Nabekura J, Nakagawa H,
A double bond-conjugated dimethylnitrobenzene-type photolabile nitric oxide donor with improved two-photon cross section,
Bioorg. Med. Chem. Lett., 25, 3172-3175, 2015.

3. Takizawa Y, Nakata R, Fukuhara K, Yamashita H, Kubodera H, Inoue H,
The 4’-hydroxyl group of resveratrol is functionally important for direct activation of PPARa,
PLoS One, 10, e0120865 (2015).
2014年業績

原著

1. Kitamura K, Ieda N, Hishikawa K, Miyata N, Fukuhara K, Nakagawa H,
Visible light-induced nitric oxide release from a novel nitrobenzene derivative cross-conjugated with a coumarin fluorophore,
Bioorg. Med. Chem. Lett., 24, 5660-5662, 2014.

2. Imai K, Nakanishi I, Ohno A, Miyata N, Matsumoto K, Fukuhara K,
Synthesis and radical-scavenging activity of a dimethyl catechin analogue,
Bioorg. Med. Chem. Lett., 24, 2582-2584, 2014.

著書

1. 福原　潔：フェノール性抗酸化物質をシーズとした高機能性分子の開発 「抗酸化素材の開発と市場」104-114 (2014) シーエムシー出版

特許出願

1. 2014-174387号、発明の名称：「新規スチルベン誘導体」、福原　潔、熊本浩樹、樋口明弘、坪田一男
2014-174332号、発明の名称：「スチルベン誘導体を有効成分とする角結膜疾患又は老視の予防及び／又は治療剤」樋口明弘、坪田一男、福原　潔

2013年業績

原著

1. Ogasawara D, Itoh Y, Tsumoto H, Kakizawa T, Mino K, Fukuhara K, Nakagawa H, Hasegawa M, Sasaki R, Mizukami T, Miyata N, Suzuki T,
Lysine-specific demethylase 1-selective inactivators: Protein targeted drug delivery mechanism,
Angew. Chem. Int. Ed. 52, 1-6, 2013.

2. Ito-Nagahata T, Kurihara C, Hasebe M, Ishii A, Yamashita K, Iwabushi M, Sonoda M, Fukuhara K, Sawada R, Matsuoka A, Fujiwawra Y,
Small molecular analogues from resveratrol improve insulin resistance through the activation of AMPK, Biosci. Biotechnol. Biochem. 77, 1229-1235, 2013.

3. Fukuhara K, Ohno A, Ota Y, Senoo Y, Okuda H, Kurihara M, Okuno A, Niida S, Saito Y, Takikawa O,
NMR-based metabolomics of urine in a mouse model of Alzheimer’s disease: Identification of oxidative stress biomarkers,
J. Clin. Biochem. Nutr. 52, 133-138, 2013.

4. Kubota Y, Kaneda Y, Haraguchi K, Mizuno M, Abe H, Shuto S, Hamasaki T, Baba M, Tanaka H,
Synthesis of nogel 4’-C-methyl-1,3’-dioxolane pyrimidime nucleosides and evaluation of its anti-HIV=1 activity,
Tetrahedron, 69, 10884-10892, 2013

5. Indo P H, Nakanishi I, Ohkubo K, Yen H-C, Nyui M, Manda S, Matsumoto K, Fukuhara K, Anzai K, Matsui H, Nakajima A, Ichikawa H, Fukuzumi S, Ozawa T, Mukai C, Majima H,
Comparison of in vivo and in vitro antioxidative parameters for eleven food factors,
RSC Advances, 3, 4535-4538, 2013.