Structure-activity relationship studies on the THF ring moiety of acetogenin analogs for the discovery of novel anticancer agents

2022 Fiscal Year Final Research Report

• Project/Area Number: 16K08330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Kojima Naoto 京都薬科大学, 薬学部, 准教授 (90420413)
• Co-Investigator(Kenkyū-buntansha): 山下 正行 京都薬科大学, 薬学部, 教授 (20239982) ; 岩崎 宏樹 京都薬科大学, 薬学部, 助教 (70582592)
• Project Period (FY): 2016-04-01 – 2023-03-31
• Keywords: 抗がん剤 / バンレイシ科アセトゲニン類 / 構造活性相関研究 / 有機合成化学 / 生物活性物質

Outline of Final Research Achievements

Recent estimates suggest that approximately half of men and one-third of women in Japan face a potential risk of developing cancer during their lifetime. Consequently, developing practical therapeutic approaches holds immense importance for pharmaceutical scientists. Our research specifically focused on modifying Annonaceous acetogenins, a natural product category. By substituting the γ-lactone ring with a thiophene ring, our modified analog showcased promising effectiveness against cancer. However, the specific correlations between their structure and activity have remained undisclosed. Therefore, our study investigated the structure-activity relationship comprehensively, with particular emphasis on the THF ring component. Our findings underscore the significance of the relative configuration at positions C15-16 for its activity. Additionally, we discovered a novel analog with a simplified THF structure, exhibiting activity comparable to the original compound.

Free Research Field

医薬品化学

Academic Significance and Societal Importance of the Research Achievements

日本人の多くがその生涯のうちに罹患する可能性のある「がん」に対して、抗がん剤による治療は重要なアプローチの一つであるが、現時点では全てのがんに有効な薬剤の開発は困難であり、新しいメカニズムによる抗がん剤の開発が望まれている。我々は、独自のアプローチにより合成した新規なアセトゲニン誘導体が、ヒトのがん細胞の増殖を強力に抑制することを見出した。本誘導体は既存の抗がん剤にないメカニズムによりその効果を示しており、これまでにない新しい治療戦略に繋がることが期待される。