2023 Fiscal Year Final Research Report
ynthetic study of a naturally-occurring quorum sensing inhibitor and its application to developing a novel antibacterial agent with low risk of generating drug resistant bacteria
| Project/Area Number |
20KK0345
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2021 – 2023
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| Keywords | quorum sensing inhibitor |
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| Outline of Final Research Achievements |
Quorum sensing (QS) is a chemical communication process between bacteria. Inhibitors of QS could prevent bacteria from causing disease without directly affecting bacterial growth, e.g., by influencing the expression of virulence factors and biofilm formation.
In this research project, aiming at developing novel promising therapeutic agents which are less likely to induce drug-resistance, we studied chemical syntheses of naturally occurring QS inhibitors, aculenes and leotiomycines. The former compounds exhibit QS inhibitory activity against the opportunistic pathogen bacterium Chromobacterium violaceum and the latter against methicillin-resistant Staphylococcus aureus (MRSA). As for the synthetic study of aculenes, norsesquiterpenoids isolated from the culture broth of Aspergillus sp. and that of Penicillium sp., we have accomplished the first total synthesis of aculenes B and D. This result was featured on ChemistryViews, the science news magazine of Chemistry Europe.
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| Free Research Field |
天然物化学，有機合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
薬剤耐性菌が発生しにくい治療薬を創成する取り組みは人類にとって喫緊の課題となっている。クォラムセンシング（QS）は菌がシグナル物質を分泌・感知することにより同種他個体の生育密度を感知する機構であり，これにより病原因子等の産生に関わる遺伝子が制御されている。これを阻害する物質は，菌に選択圧をかけずに菌体間の交信を撹乱するため耐性菌が発生しにくいと考えられ，新たな感染症治療薬の候補化合物になる可能性がある。
本研究では，病原菌のQS機構を阻害する天然有機化合物を新規感染症治療薬のリード化合物として利用することを志向して，それらの化学合成法の開発と応用研究に向けた有機合成化学的研究を実施した。
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