dc.contributor.author | Palanimuthu, Duraippandi | |
dc.contributor.author | Wu, Zhixuan | |
dc.contributor.author | Jansson, Patric J | |
dc.contributor.author | Braidy, Nady | |
dc.contributor.author | Bernhardt, Paul V | |
dc.contributor.author | Richardson, Des R | |
dc.contributor.author | Kalinowski, Danuta S | |
dc.date.accessioned | 2021-09-21T05:48:36Z | |
dc.date.available | 2021-09-21T05:48:36Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 1477-9226 | |
dc.identifier.doi | 10.1039/c8dt01099d | |
dc.identifier.uri | http://hdl.handle.net/10072/408185 | |
dc.description.abstract | Alzheimer'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.peerreviewed | Yes | |
dc.language | English | |
dc.publisher | Royal Society of Chemistry | |
dc.relation.ispartofpagefrom | 7190 | |
dc.relation.ispartofpageto | 7205 | |
dc.relation.ispartofissue | 21 | |
dc.relation.ispartofjournal | Dalton Transactions | |
dc.relation.ispartofvolume | 47 | |
dc.subject.fieldofresearch | Inorganic chemistry | |
dc.subject.fieldofresearch | Theoretical and computational chemistry | |
dc.subject.fieldofresearch | Other chemical sciences | |
dc.subject.fieldofresearchcode | 3402 | |
dc.subject.fieldofresearchcode | 3407 | |
dc.subject.fieldofresearchcode | 3499 | |
dc.subject.keywords | Science & Technology | |
dc.subject.keywords | Physical Sciences | |
dc.subject.keywords | Chemistry, Inorganic & Nuclear | |
dc.subject.keywords | Chemistry | |
dc.subject.keywords | IRON OVERLOAD DISEASE | |
dc.title | Novel chelators based on adamantane-derived semicarbazones and hydrazones that target multiple hallmarks of Alzheimer's disease | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Palanimuthu, 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.updated | 2021-09-21T05:46:57Z | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Richardson, Des R. | |