Elucidation of an action mechanism of BNTX derivatives toward antitrichomonal activity and the structure activity relationship
| Project/Area Number |
17K13259
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
KUTSUMURA Noriki 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (00439241)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 抗トリコモナス活性 / 構造活性相関 / オピオイド / 原虫感染症治療薬 / BNTX / チオール捕捉能 / Favorskii型転位 / 4,5-エポキシモルヒナン / モルヒナン / ノルモルヒナン / Favorskii転位反応 / 鎮痛 / モルヒナン骨格 / トリコモナス症治療薬 / 有機化学 / 合成化学 / 感染症 / 生理活性 / 薬学 |
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| Outline of Final Research Achievements |
This study was conducted with the aim of clarifying the action mechanism of antitrichomonal activity of 7-benzylidenenaltrexone (BNTX) derivatives, which are known as delta-opioid receptor antagonists. A variety of BNTX derivatives were synthesized, and then, their antitrichomonal activity and opioid receptor binding affinity were evaluated. As a result, it was found that there was not much correlation between the antitrichomonal activity and the affinity of the opioid receptor. On the other hand, it was confirmed that the conjugated double bond in BNTX derivatives was an important factor for the expression of antitrichomonal activity as well as antimalarial activity. In addition, a novel Favorskii-type rearrangement reaction of the 4,5-epoxymorphinan compounds was discovered in the process of synthesis of BNTX derivatives.
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| Academic Significance and Societal Importance of the Research Achievements |
トリコモナス症は、T. vaginalisという原虫によって引き起こされる性感染症の一つで、毎年世界で1億人以上の新規感染者が報告されている。我が国ではメトロニダゾールが第一選択薬として用いられているが、近年は耐性株も報告されており、新規作用機序の治療薬の開発が望まれている。本研究で見出したBNTX誘導体は中程度の抗トリコモナス活性を有しており、トリコモナスの抗酸化系を阻害するという新しい活性発現メカニズムが提案された。実際、メトロニダゾールはT. vaginalisにもリスザルのT. mobilensisにも殺活性を示したが、BNTX誘導体はT. vaginalisにのみ殺活性を示した。
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Report
(3 results)
Research Products
(9 results)
