DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jones, Michael R. | ko |
dc.contributor.author | Mathieu, Emilie | ko |
dc.contributor.author | Dyrager, Christine | ko |
dc.contributor.author | Faissner, Simon | ko |
dc.contributor.author | Vaillancourt, Zavier | ko |
dc.contributor.author | Korshavn, Kyle J. | ko |
dc.contributor.author | Lim, Mi Hee | ko |
dc.contributor.author | Ramamoorthy, Ayyalusamy | ko |
dc.contributor.author | Yong, V. Wee | ko |
dc.contributor.author | Tsutsui, Shigeki | ko |
dc.contributor.author | Stys, Peter K. | ko |
dc.contributor.author | Storr, Tim | ko |
dc.date.accessioned | 2018-02-21T06:05:39Z | - |
dc.date.available | 2018-02-21T06:05:39Z | - |
dc.date.created | 2018-02-08 | - |
dc.date.created | 2018-02-08 | - |
dc.date.issued | 2017-08 | - |
dc.identifier.citation | CHEMICAL SCIENCE, v.8, no.8, pp.5636 - 5643 | - |
dc.identifier.issn | 2041-6520 | - |
dc.identifier.uri | http://hdl.handle.net/10203/240255 | - |
dc.description.abstract | Alzheimer's disease (AD) is a multifactorial disease that is characterized by the formation of intracellular neurofibrillary tangles and extracellular amyloid-beta (A beta) plaque deposits. Increased oxidative stress, metal ion dysregulation, and the formation of toxic A beta peptide oligomers are all considered to contribute to the etiology of AD. In this work we have developed a series of ligands that are multi-target-directed in order to address several disease properties. 2-(1-(3-Hydroxypropyl)-1H-1,2,3-triazol-4-yl) phenol (POH), 2-(1-(2-morpholinoethyl)-1H-1,2,3-triazol-4-yl) phenol (PMorph), and 2-(1-(2-thiomorpholinoethyl)-1H-1,2,3-triazol-4-yl) phenol (PTMorph) have been synthesized and screened for their antioxidant capacity, Cu-binding affinity, interaction with the A beta peptide and modulation of A beta peptide aggregation, and the ability to limit A beta(1-42)-induced neurotoxicity in human neuronal culture. The synthetic protocol and structural variance incorporated via click chemistry, highlights the influence of R-group modification on ligand-A beta interactions and neuroprotective effects. Overall, this study demonstrates that the phenoltriazole ligand scaffold can target multiple factors associated with AD, thus warranting further therapeutic development. | - |
dc.language | English | - |
dc.publisher | ROYAL SOC CHEMISTRY | - |
dc.subject | AMYLOID-BETA-PEPTIDE | - |
dc.subject | A-BETA | - |
dc.subject | SMALL MOLECULES | - |
dc.subject | NEURODEGENERATIVE DISEASES | - |
dc.subject | A-BETA(42) PEPTIDE | - |
dc.subject | CELLULAR TOXICITY | - |
dc.subject | TERMINAL ALKYNES | - |
dc.subject | FIBRIL FORMATION | - |
dc.subject | ROS PRODUCTION | - |
dc.subject | AGGREGATION | - |
dc.title | Multi-target-directed phenol-triazole ligands as therapeutic agents for Alzheimer's disease | - |
dc.type | Article | - |
dc.identifier.wosid | 000406103100046 | - |
dc.identifier.scopusid | 2-s2.0-85026256755 | - |
dc.type.rims | ART | - |
dc.citation.volume | 8 | - |
dc.citation.issue | 8 | - |
dc.citation.beginningpage | 5636 | - |
dc.citation.endingpage | 5643 | - |
dc.citation.publicationname | CHEMICAL SCIENCE | - |
dc.identifier.doi | 10.1039/c7sc01269a | - |
dc.contributor.localauthor | Lim, Mi Hee | - |
dc.contributor.nonIdAuthor | Jones, Michael R. | - |
dc.contributor.nonIdAuthor | Mathieu, Emilie | - |
dc.contributor.nonIdAuthor | Dyrager, Christine | - |
dc.contributor.nonIdAuthor | Faissner, Simon | - |
dc.contributor.nonIdAuthor | Vaillancourt, Zavier | - |
dc.contributor.nonIdAuthor | Korshavn, Kyle J. | - |
dc.contributor.nonIdAuthor | Ramamoorthy, Ayyalusamy | - |
dc.contributor.nonIdAuthor | Yong, V. Wee | - |
dc.contributor.nonIdAuthor | Tsutsui, Shigeki | - |
dc.contributor.nonIdAuthor | Stys, Peter K. | - |
dc.contributor.nonIdAuthor | Storr, Tim | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | AMYLOID-BETA-PEPTIDE | - |
dc.subject.keywordPlus | A-BETA | - |
dc.subject.keywordPlus | SMALL MOLECULES | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | A-BETA(42) PEPTIDE | - |
dc.subject.keywordPlus | CELLULAR TOXICITY | - |
dc.subject.keywordPlus | TERMINAL ALKYNES | - |
dc.subject.keywordPlus | FIBRIL FORMATION | - |
dc.subject.keywordPlus | ROS PRODUCTION | - |
dc.subject.keywordPlus | AGGREGATION | - |
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