Development of novel antibacterial drug leads based on library synthesis strategy accelerating natural product drug discovery

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20704
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Yamamoto Kazuki 北海道大学, 薬学研究院, 助教 (50955127)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 天然物創薬 / ライブラリー合成 / 抗菌薬

Outline of Final Research Achievements

The global spread of drug-resistant bacteria is becoming a worldwide issue, and there is a strong demand for the development of new antibiotics that are effective against drug-resistant bacteria. In this study, I aimed to obtain novel analogues with improved antibacterial activity than parent MraY inhibitory natural products, mureidomycin and capuramycin, using a natural product analogue library synthesis strategy that simplifies the analogue synthesis established in previous studies. As a result of evaluating the MraY inhibitory activity and antibacterial activity of about 300 analogues, I obtained analogues with stronger MraY inhibitory activity than natural products and analogues that exhibit antibacterial activity against different bacterial species than natural products. In addition, I expanded the fragments used in library synthesis in order to obtain analogues with improved antibacterial activity.

Free Research Field

創薬化学、天然物化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、構造が複雑な天然物の誘導体合成を加速化するライブラリー合成法を用いて、抗菌活性を示すMraY阻害天然物ムレイドマイシンおよびカプラマイシンの構造最適化を行った。これらの天然物を基にして約300種の誘導体を合成し、抗菌活性が向上した誘導体が複数得られた。本研究により見出された誘導体は、薬剤耐性菌に対抗するための新規抗菌薬開発の一助となることが期待できる。