Abstract:
:Copper and zinc have been found to contribute to the burden of amyloid-β (Aβ) aggregations in neurodegenerative Alzheimer's disease (AD). Dysregulation of these metals leads to the generation of reactive oxygen species (ROS) and eventually results in oxidative damage and accumulation of the Aβ peptide, which are the key elements of the disease. Aiming to pursue the discovery of new modulators for the disease, we here rationally focused on conjugating the core hydroxyquinoline of the metal-protein attenuating compound PBT2 and the N-methylanilide analogous moiety of the Aβ imaging agent to build a new type of multi-target modulators of Aβ aggregations. We found that the N,N-dimethylanilinyl imines 7a, 8a, and the corresponding amines 7b, 8b exerted efficient inhibition of Cu(2+) - or Zn(2+) -induced Aβ aggregations and significant disassembly of metal-mediated Aβ aggregated fibrils. Further, 7a and 7b also exhibited significant ROC scavenging effects compared to PBT2. The results suggested that 7a and 7b are promising lead compounds for the development of a new therapy for AD.
journal_name
Arch Pharm (Weinheim)journal_title
Archiv der Pharmazieauthors
Fu CL,Hsu LS,Liao YF,Hu MKdoi
10.1002/ardp.201500453subject
Has Abstractpub_date
2016-05-01 00:00:00pages
327-41issue
5eissn
0365-6233issn
1521-4184journal_volume
349pub_type
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journal_title:Archiv der Pharmazie
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