Design, synthesis, and biological evalution of the novel atpenin A5 derivatives as a nematode commlex II inhibitor

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kitasato University
• Principal Investigator: Arima Shiho 北里大学, 薬学部, 助教 (20276158)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 医薬品化学 / 構造活性相関

Outline of Final Research Achievements

Atpenin A5 (1) was isolated from the fermentation broth of a fungal strain, Penicillium sp. FO-125, and was demonstrated to exhibit potent complex II inhibitory activity. Therefore, 1 is of interest as a new anthelmintic agent. However, the production level of 1 in culture was low, and it exhibited the same inhibitory activity towards both nematode and mammalian complex II. To introduce selectivity towards nematode complex II, a novel atpenin A5 derivatives were designed and synthesized. In this study, the author was reported in detail the design, synthesis, and biological evaluation of the novel atpenin A5 derivatives.

Free Research Field

薬学・創薬化学

Academic Significance and Societal Importance of the Research Achievements

強力なcomplex II阻害活性を有するatpenin A5を基盤とする新規抗寄生虫薬の開発を目指し、極めて効率的に、かつ理論的に独創的な創薬研究を進めることで、世界的に要望の高い新しいタイプの抗寄生虫薬の開発の実現に向けて重要な知見をもたらすことができた。また、得られる結果は創薬化学研究分野において、学術的に非常に価値のあるものになると考えている。