Drug discovery reseach for a novel antibiotic compound though clusterization of natural products

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07708
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Tohoku University
• Principal Investigator: Masaru Enomoto 東北大学, 農学研究科, 准教授 (90546342)
• Co-Investigator(Renkei-kenkyūsha): Konoki Keiichi ; Kitagawa Wataru
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: クラスター効果 / monensin / イオンチャネル

Outline of Final Research Achievements

Monensin (Mon) is an ionophore natural product exhibiting potent cytotoxic activity. Meanwhile, computational analysis anticipated that its methyl ester (MME) might act as an ion channel when MMEs aggregate to be an octamer. This result would suggest that clusterization of bioactive compounds might change their mechanism of activity, by which the intensity of activity of some bioactive natural products could also be improved compared to the original compounds. Thus, we embarked on the synthetic study of a monensin octamer to prove the anticipation. If this methodology could be applied to various bioactive compounds, this can lead to a novel concept for drug discovery research.

Free Research Field

天然物化学，有機合成化学

Academic Significance and Societal Importance of the Research Achievements

薬剤（多剤）耐性菌への対処は人類にとって喫緊の課題となっている。その一方で，新たに開発される（発見される）薬剤の種類は頭打ちの傾向にあり，新たな創薬方法論の開発が期待される。これまでは化学構造の変換による方法がもっぱら実施されていたが，物理的な効果により既存の天然物の活性強度を簡便に強化できれば, 無名の低活性天然物が強力な抗菌剤へと生まれ変わる可能性がある。これにより，薬剤候補化合物数の増加に貢献できるとともに，既存の化学構造改変法と異なる新たな創薬方法論を提示できる。