期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 6, 期 9, 页码 1025-1029出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.5b00281
关键词
8-Hydroxyquinoline; metal ionophore; positron emission tomography; Alzheimer's disease
资金
- NIDA NIH HHS [K01 DA038000] Funding Source: Medline
Zinc, copper, and iron ions are involved in amyloid-beta (A beta) deposition and stabilization in Alzheimer's disease (AD). Consequently, metal binding agents that prevent metal-A beta interaction and lead to the dissolution of A beta deposits have become well sought therapeutic and diagnostic targets. However, direct intervention between diseases and metal abnormalities has been challenging and is partially attributed to the lack of a suitable agent to determine and modify metal concentration and distribution in vivo. In the search of metal ionophores, we have identified several promising chemical entities by strategic fluorination of 8-hydroxyquinoline drugs, clioquinol, and PBT2. Compounds 15-17 and 28-30 showed exceptional metal ionophore ability (6-40-fold increase of copper uptake and >2-fold increase of zinc uptake) and inhibition of zinc induced A beta oligomerization (EC(50)s < similar to 5 mu M). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with F-18.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据