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dc.contributor.authorPalanimuthu, Duraippandi
dc.contributor.authorWu, Zhixuan
dc.contributor.authorJansson, Patric J
dc.contributor.authorBraidy, Nady
dc.contributor.authorBernhardt, Paul V
dc.contributor.authorRichardson, Des R
dc.contributor.authorKalinowski, Danuta S
dc.date.accessioned2021-09-21T05:48:36Z
dc.date.available2021-09-21T05:48:36Z
dc.date.issued2018
dc.identifier.issn1477-9226
dc.identifier.doi10.1039/c8dt01099d
dc.identifier.urihttp://hdl.handle.net/10072/408185
dc.description.abstractAlzheimer's disease (AD) is characterized by multiple pathological hallmarks, including β-amyloid aggregation, oxidative stress, and metal dys-homeostasis. In the absence of treatments addressing its multi-factorial pathology, we designed novel multi-functional adamantane-based semicarbazones and hydrazones (1-12) targeting AD hallmarks. Of these, 2-pyridinecarboxaldehyde (N-adamantan-1-yl)benzoyl-4-amidohydrazone (10) was identified as the lead compound, which demonstrated: (1) pronounced iron chelation efficacy; (2) attenuation of CuII-mediated β-amyloid aggregation; (3) low cytotoxicity; (4) inhibition of oxidative stress; and (5) favorable characteristics for effective blood-brain barrier permeation. Structure-activity relationships revealed that pyridine-derived hydrazones represent a promising pharmacophore for future design strategies due to their ability to bind critical FeII pools. Collectively, the unique multi-functional activity of these agents provides a novel therapeutic strategy for AD treatment.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherRoyal Society of Chemistry
dc.relation.ispartofpagefrom7190
dc.relation.ispartofpageto7205
dc.relation.ispartofissue21
dc.relation.ispartofjournalDalton Transactions
dc.relation.ispartofvolume47
dc.subject.fieldofresearchInorganic chemistry
dc.subject.fieldofresearchTheoretical and computational chemistry
dc.subject.fieldofresearchOther chemical sciences
dc.subject.fieldofresearchcode3402
dc.subject.fieldofresearchcode3407
dc.subject.fieldofresearchcode3499
dc.subject.keywordsScience & Technology
dc.subject.keywordsPhysical Sciences
dc.subject.keywordsChemistry, Inorganic & Nuclear
dc.subject.keywordsChemistry
dc.subject.keywordsIRON OVERLOAD DISEASE
dc.titleNovel chelators based on adamantane-derived semicarbazones and hydrazones that target multiple hallmarks of Alzheimer's disease
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationPalanimuthu, D; Wu, Z; Jansson, PJ; Braidy, N; Bernhardt, PV; Richardson, DR; Kalinowski, DS, Novel chelators based on adamantane-derived semicarbazones and hydrazones that target multiple hallmarks of Alzheimer's disease, Dalton Transactions, 2018, 47 (21), pp. 7190-7205
dc.date.updated2021-09-21T05:46:57Z
gro.hasfulltextNo Full Text
gro.griffith.authorRichardson, Des R.


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