Search for seed molecules for development of new antitumor drugs from plant alkaloids

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03993
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Chiba University
• Principal Investigator: KITAJIMA Mariko 千葉大学, 大学院薬学研究院, 准教授 (60195261)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 天然活性物質 / 生物活性物質の探索 / アルカロイド / 化学合成 / 構造解析

Outline of Final Research Achievements

Total synthesis of gelsedine-type Gelsemium alkaloids which have cytotoxic activity toward human cancer cell lines were carried out and asymmetric total synthesis of seven alkaloids was accomplished. New alkaloids were isolated from medicinal plant resources. New cyclic tetrapeptide was isolated from Ophiorrhiza plant and its asymmetric total synthesis was accomplished. Some cyclic tetrapeptide derivatives possessing cytotoxicity toward human cancer cell lines were obtained via the structure－activity relationship study.

Free Research Field

天然資源系薬学

Academic Significance and Societal Importance of the Research Achievements

がんの罹患数やがんによる死亡数は増加し続けており、新たな抗がん剤の開発が望まれている。本研究では、薬用資源植物からの新規抗腫瘍性アルカロイドの探索、天然アルカロイド類の全合成、誘導体合成、活性評価を実施し、ヒト腫瘍細胞毒性作用を有する化合物や新規天然アルカロイド類の取得、詳細な活性評価に向けた微量アルカロイド類の不斉全合成を達成した。今後、これらアルカロイドの活性評価、構造活性相関研究等を通して新規抗腫瘍薬開発に向けたシード分子の取得が期待できる。