• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2018 Fiscal Year Final Research Report

Design, synthesis and evaluation of curcumin analogues toward amyloid peptide aggregation inhibition and detection

Research Project

  • PDF
Project/Area Number 16K07709
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bioorganic chemistry
Research InstitutionYamagata University

Principal Investigator

Konno Hiroyuki  山形大学, 大学院理工学研究科, 教授 (50325247)

Project Period (FY) 2016-04-01 – 2019-03-31
Keywordsアミロイドβ / 凝集阻害剤 / 蛍光検出剤 / クルクミン / 水溶性 / 細胞毒性 / ラジカルスカベンジャー / ドッキングシミレーション
Outline of Final Research Achievements

A structure activity relationship study of curcumin analogues for the inhibition of amyloid be-ta aggregation is investigated. We optimized the o-phenol and olefin spacer and resulted in the identification of the C5-monoketone type curcumin analogue AY1319, which exhibited potent anti-amyloid be-ta aggregation activity, sufficient water solubility, and low cytotoxicity. Inhibited amyloid be-ta aggregation lead to nanorod-like fragments by TEM analysis. On the other hand, we found that curcumin analogues with the fluorescence property instead of non-inhibition of amyloid be-ta fibrils. Me-CUR shows excellent fluorescence, especially higher than ThT, in the presence of amyloid be-ta fibrils. These results suggest that Me-CUR can become a useful in vitro amyloid fluorescence sensor for diagnosis of Alzheimer’s disease. The docking simulation showed that Me-CUR located in the inner site of amyloid be-ta fibrils and AY1319 located in the outer site.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病は認知機能の低下を伴う脳神経変性疾患であり、患者数は増加の一途をたどっている。世界中で治療薬開発が試みられているにも関わらず根本治療薬はない。筆者は食物由来クルクミンに治療効果が示されて以来、治療薬としての可能性を試みてきた。結果的に難水溶性物質を薬物動態可能な状態まで水溶性を向上させることに成功した。同時にアミロイドベータ凝集体の阻害能の向上にも成功している。一方でアミロイドベータ凝集体の蛍光検出にも成功している。臨床応用には道半ばであるが、人類の福祉に貢献すべく一歩を踏み出せたと考えている。

URL: 

Published: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi