Analysis of the mechanism of action of phomopsin toward the development of anti-cancer molecule

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K14629
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Yasuno Yoko 九州大学, 理学研究院, 助教 (40736500)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ホモプシン / 抗がん / 作用機序

Outline of Final Research Achievements

Phomopsin A is a natural product isolated as a causative agent of food poisoning in cattle, sheep, and other livestock. Since it strongly inhibits tubulin polymerization, it has been expected to be a lead for new anticancer drugs. However, comparison of its activity with that of its recently isolated natural congener, phomopsin F, suggests that phomopsin may have an unknown mechanism of activity other than tubulin polymerization inhibition. In this study, we aimed to elucidate the mechanism of action of phomopsins by the total synthesis of phomopsins and a structure-activity relationship study on the side-chain moiety. As a result, we succeeded in synthesizing the cyclic moiety of pshomopsins and its side-chain analogues.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

ホモプシン類は歴史的にも古い天然物であり、その標的分子がチューブリンであることは
定説となっていた。本研究は、新規な抗がん剤開発の可能性を秘めた基礎研究として、さらには、がん克服と健康社会の構築に寄与する学術的・社会的意義を備えている。さらに研究を進めることによって新たな活性発現機序の存在を明らかにできれば、これまでの定説を覆す研究成果として注目を集めるものと期待される。