Elucidation of the mechanism of antinematode activity of deoxy-rare sugars

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38040:Bioorganic chemistry-related
• Research Institution: Kagawa University
• Principal Investigator: Sato Masashi 香川大学, 農学部, 教授 (20263890)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 希少糖 / 抗線虫薬 / Caenorhabditis elegans

Outline of Final Research Achievements

We reported that the deoxy-rare sugar 1-deoxy-D-allulose (1d-Alu) strongly inhibits the growth of the nematode Caenorhabditis elegans, inspiring the idea that 1d-Alu could be an antinematode drug with an inhibitory point in sugar metabolism. In this study, we aimed to clarify the mechanism of action of 1d-Alu. We synthesized 1d-Alu and performed HPLC analysis of 1d-Alu-treated nematode extracts. As a result, 1d-Alu was incorporated into the nematode body, and peaks presumed to be 6-phosphate was detected. From the above results, it is considered that the biological activity of 1d-Alu is caused by the inhibition of sugar metabolism by its metabolite.

Free Research Field

Bioorganc chemisty

Academic Significance and Societal Importance of the Research Achievements

生物活性をもつ希少糖が生体内でどのように代謝され，どのように働くのかについて，現在までほとんど知見がない。糖代謝経路は，原核生物からヒトまで広く遺伝的に保存されているため，人畜への毒性が懸念され，薬剤ターゲットとは考えられてこなかった。しかし，本研究により，糖の取り込みや解糖系をターゲットとした新奇な作用メカニズムをもつ抗線虫薬の開発が実現できれば，熱帯医学，獣医学分野への学術的，社会的な意義が大きいと考えられる。