2021 Fiscal Year Final Research Report
Development of lead discovery platform accelerating medicinal chemistry based on natural products
| Project/Area Number |
19H03345
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 抗がん剤 / 抗菌剤 / 天然物 |
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| Outline of Final Research Achievements |
The major skeleton of a natural product was used as the "core" structure and various acylhydrazines as "accessories." Both fragments were reacted on a 96-well plate, and the progress and yield of the hydrazone formation reaction were confirmed in each well by LC-MS. The reaction conditions for hydrazone formation and the stability of the hydrazones under the same conditions were also examined under the conditions of biological activity evaluation using both fragments. Using this method, a library of derivatives of several natural products was synthesized in parallel. As a result, we identified several derivatives that surpassed the activity of the original natural products, including a derivative that is extremely effective against drug-resistant bacteria.
Translated with www.DeepL.com/Translator (free version)
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
天然物そのものが医薬品となるケースはわずか数％にすぎず、薬の「原石」を創薬リードとするためには、生物活性の増強・標的に対する選択性の向上・代謝安定性の付与・体内動態の向上・毒性の低減などの様々な性質を改善する必要がある。そのためには、天然物が有する化学構造の改変が必須であり、多彩な天然物誘導体群（ライブラリー）を用いた構造活性相関の検討が必要である。変研究では、天然物ライブラリーの迅速合成法の開発と、それを用いた抗がん剤、抗菌剤リードの開発を行うもので、本研究を通して得られた生物活性化合物は、人類の健康福祉の維持・向上へ大きく貢献する。
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