Novel fluorinated 8-hydroxyquinoline based metal Ionophores for exploring the metal hypothesis of alzheimer’s disease

Simple item page
dc.contributor.authorLiang, SHen_AU
dc.contributor.authorSouthon, AGen_AU
dc.contributor.authorFraser, BHen_AU
dc.contributor.authorKrause-Heuer, AMen_AU
dc.contributor.authorZhang, Ben_AU
dc.contributor.authorShoup, TMen_AU
dc.contributor.authorLewis, Ren_AU
dc.contributor.authorVolitakis, Ien_AU
dc.contributor.authorHan, Yen_AU
dc.contributor.authorGreguric, Ien_AU
dc.contributor.authorBush, AIen_AU
dc.contributor.authorVasdev, Yen_AU
dc.date.accessioned2020-03-23T23:53:45Zen_AU
dc.date.available2020-03-23T23:53:45Zen_AU
dc.date.issued2015-08-10en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractZinc, copper, and iron ions are involved in amyloid-beta (Aβ) deposition and stabilization in Alzheimer’s disease (AD). Consequently, metal binding agents that prevent metal-Aβ interaction and lead to the dissolution of Aβ 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 Aβ oligomerization (EC50s < ∼5 μM). These compounds are suitable for further development as drug candidates and/or positron emission tomography (PET) biomarkers if radiolabeled with 18F. © 2015 American Chemical Societyen_AU
dc.identifier.citationLiang, S. H., Southon, A. G., Fraser, B. H., Krause-Heuer, A. M., Zhang, B., Shoup, T. M., Lewis, R., Volitakis, I., Han, Y., Greguric, I., Bush, A. I., &. Vasdev, N. (2015). Novel fluorinated 8-hydroxyquinoline based metal ionophores for exploring the metal hypothesis of Alzheimer’s disease. ACS Medicinal Chemistry Letters, 6(9), 1025-1029. doi:10.1021/acsmedchemlett.5b00281en_AU
dc.identifier.govdoc8803en_AU
dc.identifier.issn1948-5875en_AU
dc.identifier.issue9en_AU
dc.identifier.journaltitleACS Medicinal Chemistry Lettersen_AU
dc.identifier.pagination1025-1029en_AU
dc.identifier.urihttp://dx.doi.org/10.1021/acsmedchemlett.5b00281en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9206en_AU
dc.identifier.volume6en_AU
dc.language.isoenen_AU
dc.publisherAmerican Chemical Societyen_AU
dc.subjectReaction product transport systemsen_AU
dc.subjectMetalsen_AU
dc.subjectCentral nervous systemen_AU
dc.subjectAgglomerationen_AU
dc.subjectDrugsen_AU
dc.subjectDiseasesen_AU
dc.subjectAgingen_AU
dc.subjectEmission computed tomographyen_AU
dc.titleNovel fluorinated 8-hydroxyquinoline based metal Ionophores for exploring the metal hypothesis of alzheimer’s diseaseen_AU
dc.typeJournal Articleen_AU
Files
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles