Kurisawa, Naoaki

写真a

Affiliation

Faculty of Science and Technology, Department of Chemistry (Yagami)

Position

Assistant Professor (Non-tenured)/Research Associate (Non-tenured)/Instructor (Non-tenured)

Career 【 Display / hide

  • 2021.03
    -
    2022.09

    Japan Society for the Promotion of Science

  • 2022.10
    -
    2023.03

    Japan Society for the Promotion of Science

  • 2023.04
    -
    Present

    慶應義塾大学 理工学部 化学科 助教(有期)

Academic Background 【 Display / hide

  • 2010.04
    -
    2013.03

    岩手県立盛岡第一高校

  • 2013.04
    -
    2017.03

    岩手大学 農学部 応用生物化学課程

  • 2017.04
    -
    2019.03

    岩手大学大学院 総合科学研究科 農学専攻

  • 2019.04
    -
    2022.09

    慶應義塾大学大学院 理工学研究科

 

Research Areas 【 Display / hide

  • Life Science / Bioorganic chemistry

Research Keywords 【 Display / hide

  • ケミカルバイオロジー

  • Natural Products Chemistry

  • 海洋天然物

 

Papers 【 Display / hide

  • Isolation and Structure Determination of Akunolides, Macrolide Glycosides from a Marine Okeania sp. Cyanobacterium

    Kairi Umeda, Arihiro Iwasaki, Raimu Taguchi, Naoaki Kurisawa, Ghulam Jeelani, Tomoyoshi Nozaki, Kiyotake Suenaga

    Journal of Natural Products 86 ( 11 ) 2529 - 2538 2023.11

    ISSN  0163-3864

  • Total synthesis of acetylene-containing lipopeptides odookeanynes A and B

    Yung-Han Lo, Kairi Umeda, Naoaki Kurisawa, Ghulam Jeelani, Tomoyoshi Nozaki, Kiyotake Suenaga

    Tetrahedron Letters (Tetrahedron Letters)  130 2023.10

    ISSN  00404039

     View Summary

    The total synthesis of acetylene-containing lipopeptides odookeanynes A (1) and B (2), isolated from the marine cyanobacterium Okeania sp., has been achieved. A biological evaluation using synthetic odookeanynes revealed their potent antitrypanosomal activity. This report not only describes a synthetic pathway for structurally related compounds for SAR studies but also offers new insights into their potential as antiparasitic agents.

  • Fumagillin inhibits growth of the enteric protozoan parasite Entamoeba histolytica by covalently binding to and selectively inhibiting methionine aminopeptidase 2.

    Natsuki Watanabe, Yumiko Saito-Nakano, Naoaki Kurisawa, Keisuke Otomo, Kiyotake Suenaga, Kentaro Nakano, Tomoyoshi Nozaki

    Antimicrobial agents and chemotherapy 67 ( 11 ) e0056023 2023.10

    ISSN  0066-4804

     View Summary

    Amebiasis is an important cause of morbidity and mortality worldwide, and caused by infection with the protozoan parasite Entamoeba histolytica. Metronidazole is currently the first-line drug despite adverse effects and concerns on the emergence of drug resistance. Fumagillin, a fungal metabolite from Aspergillus fumigatus, and its structurally related natural and synthetic compounds have been previously explored as potential anti-angiogenesis inhibitors for cancers, anti-microbial, and anti-obese compounds. Although fumagillin was used for human amebiasis in clinical trials in 1950s, the mode of action of fumagillin remains elusive until now. In this report, we showed that fumagillin covalently binds to methionine aminopeptidase 2 (MetAP2) and non-covalently but abundantly binds to patatin family phospholipase A (PLA). Susceptibility against fumagillin of the amebic strains in which expression of E. histolytica MetAP2 (EhMetAP2) gene was silenced increased compared to control strain. Conversely, overexpression of EhMetAP2 mutants that harbors amino acid substitutions responsible for resistance to ovalicin, a fumagillin analog, in human MetAP2, also resulted in decrease in fumagillin susceptibility. In contrast, neither gene silencing nor overexpression of E. histolytica PLA (EhPLA) affected fumagillin susceptibility. These data suggest that EhPLA is not essential and not the target of fumagillin for its amebicidal activity. Taken together, our data have demonstrated that EhMetAP2 is the primary target for amebicidal activity of fumagillin, and EhMetAP2 represents a rational explorable target for the development of alternative therapeutic agents against amebiasis.

  • Allelopathic Potential of Marsdenia tenacissima (Roxb.) Moon against Four Test Plants and the Biological Activity of Its Allelopathic Novel Compound, 8-Dehydroxy-11β-O-Acetyl-12β-O-Tigloyl-17β-Marsdenin

    Moh S.M., Kurisawa N., Suenaga K., Kato-Noguchi H.

    Plants (Plants)  12 ( 8 )  2023.04

     View Summary

    Plant parts and extracts that are rich in bioactive substances with allelopathic potential can be explored as a possible alternative to herbicides for natural weed control in sustainable agriculture. In the present study, we investigated the allelopathic potential of Marsdenia tenacissima leaves and its active substances. Aqueous methanol extracts of M. tenacissima showed significant inhibitory activities against the growth of lettuce (Lactuca sativa L.), alfalfa (Medicago sativa L.), timothy (Phleum pratense L.), and barnyard grass (Echinochloa crusgalli (L.) Beauv.). The extracts were purified through various chromatography steps, and one active substance was isolated and determined by spectral data to be a novel compound, assigned as steroidal glycoside 3 (8-dehydroxy-11β-O-acetyl-12β-O-tigloyl-17β-marsdenin). Steroidal glycoside 3 significantly inhibited the seedling growth of cress at a concentration of 0.03 mM. The concentrations needed for 50% growth inhibition of the cress shoots and roots were 0.25 and 0.03 mM, respectively. These results suggest that steroidal glycoside 3 may be responsible for the allelopathy of M. tenacissima leaves.

  • Total Synthesis of Caldorazole, a Potent Mitochondrial Respiratory Chain Inhibitor without Chiral Centers

    Miyamoto Y., Iwasaki A., Fujimura H., Kudo C., Kurisawa N., Ohno O., Suenaga K.

    Journal of Organic Chemistry (Journal of Organic Chemistry)  88 ( 5 ) 3208 - 3216 2023.03

    ISSN  00223263

     View Summary

    Caldorazole (1) is a novel polyketide that was isolated from a marine cyanobacterium in 2022. It is a unique natural product that exhibits potent inhibitory activity against mitochondrial respiratory chain complex I despite having no chiral centers. To establish a method for obtaining caldorazole without relying on biological resources and for constructing a useful synthetic route for studies of its structure-activity relationship, we achieved the first total synthesis of caldorazole using a convergent synthetic route.

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Reviews, Commentaries, etc. 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of a novel mode of action of iezoside based on the structure-activity relationship

    2023.08
    -
    2025.03

    研究活動スタート支援, Principal investigator

  • 抗トリパノソーマ活性を示す新規海洋天然物の探索と作用メカニズム解明

    2021.04
    -
    2023.03

    日本学術振興会, Grants-in-Aid for Scientific Research, Grant-in-Aid for JSPS Fellows, No Setting

     View Summary

    本年度は、海洋シアノバクテリアを由来とする新規抗トリパノソーマ活性物質の探索および作用機序解明に向けた合成研究を行った。探索研究においては、新規抗トリパノソーマ活性物質として kinenzoline および hedoamide を発見し、構造を決定した。kinenzoline は種々のスペクトル解析および全合成によって構造を確定し、トリパノソーマ原虫に対しIC50 4.5 uM と中程度の増殖阻害活性を示す一方で、ヒト正常細胞であるWI-38に対しては100 uM でも毒性を示さなかった。Hedoamide は強力な抗トリパノソーマ活性を示す一方で、WI-38 と比較し30倍程度の選択性を示した。申請者が以前発見したiheyamide A については全合成を達成し、構造活性相関研究からペプチド部の伸長と共に抗トリパノソーマ活性が増強されることを見出した。
    また、探索研究の過程で極めて強力ながん細胞増殖阻害活性を示す新規天然物 iezoside を発見した。本化合物は新規の炭素骨格を有するペプチド-ポリケチドハイブリッド配糖体であり、絶対立体配置を含む全構造を最終的に全合成によって確定した。さらに、iezoside の生物活性が強力なカルシウムポンプ阻害によって引き起こされることを明らかにした。Iezoside は新規抗がん剤リードとして有望な化合物であり、各種類縁体を合成して構造活性相関の解明に取り組んでいる。また、本化合物は抗トリパノソーマ活性も有するため、合成したライブラリーを用いてトリパノソーマ原虫に対し高い選択毒性を示す構造改変体の創出を目指している。

Intellectual Property Rights, etc. 【 Display / hide

  • キネシン阻害剤、該阻害剤を含む抗癌剤およびキネシン阻害剤のスクリーニング方法

    Date applied: 特願2018-087733  2018.04 

    Date announced: 特開2019-189590  2019.10 

    Patent

Awards 【 Display / hide

  • 慶應義塾大学大学院理工学研究科 藤原賞

    2023.03

  • 第63回天然有機化合物討論会 奨励賞(口頭発表)

    2021.09

  • 第67回トキシンシンポジウム 奨励賞

    2021.09

  • 第18回新規素材探索研究会 最優秀ポスター賞

    2019.06

 

Courses Taught 【 Display / hide

  • LABORATORY IN SCIENCE

    2024

  • LABORATORIES IN CHEMISTRY 2

    2024

  • LABORATORY IN SCIENCE

    2023

  • LABORATORIES IN CHEMISTRY 2

    2023

Courses Previously Taught 【 Display / hide

  • LABORATORY IN SCIENCE

    Keio University

    2023.04
    -
    2024.03

  • LABORATORIES IN CHEMISTRY 2

    Keio University

    2023.04
    -
    2024.03