Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer's disease

2015
journal article
article
287
dc.abstract.enAlzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid- antiaggregation activity, inhibition of -secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD.pl
dc.affiliationWydział Farmaceutyczny : Zakład Fizykochemicznej Analizy Lekupl
dc.cm.date2020-01-07
dc.cm.id69737
dc.contributor.authorSzałaj, Natalia - 140437 pl
dc.contributor.authorWięckowska, Anna - 160757 pl
dc.contributor.authorPanek, Dawid - 148623 pl
dc.contributor.authorMalawska, Barbara - 130819 pl
dc.date.accessioned2020-01-17T08:46:06Z
dc.date.available2020-01-17T08:46:06Z
dc.date.issued2015pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.additionalNa pub. aut. podpis.: Natalia Guziorpl
dc.description.number3pl
dc.description.physical373-404pl
dc.description.points40pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume22pl
dc.identifier.doi10.2174/0929867321666141106122628pl
dc.identifier.eissn1875-533Xpl
dc.identifier.issn0929-8673pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/134650
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enAlzheimer’s diseasepl
dc.subject.enantioxidantspl
dc.subject.enβ-amyloid anti-aggregation propertiespl
dc.subject.encholinesterase inhibitorspl
dc.subject.eninhibitors of β-secretasepl
dc.subject.eninhibitors of monoamine oxidase A/Bpl
dc.subject.enmulti-target-directed ligandspl
dc.subject.enneuroprotective propertiespl
dc.subtypeArticlepl
dc.titleRecent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer's diseasepl
dc.title.journalCurrent Medicinal Chemistrypl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid- antiaggregation activity, inhibition of -secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD.
dc.affiliationpl
Wydział Farmaceutyczny : Zakład Fizykochemicznej Analizy Leku
dc.cm.date
2020-01-07
dc.cm.id
69737
dc.contributor.authorpl
Szałaj, Natalia - 140437
dc.contributor.authorpl
Więckowska, Anna - 160757
dc.contributor.authorpl
Panek, Dawid - 148623
dc.contributor.authorpl
Malawska, Barbara - 130819
dc.date.accessioned
2020-01-17T08:46:06Z
dc.date.available
2020-01-17T08:46:06Z
dc.date.issuedpl
2015
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.additionalpl
Na pub. aut. podpis.: Natalia Guzior
dc.description.numberpl
3
dc.description.physicalpl
373-404
dc.description.pointspl
40
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
22
dc.identifier.doipl
10.2174/0929867321666141106122628
dc.identifier.eissnpl
1875-533X
dc.identifier.issnpl
0929-8673
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/134650
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.subject.enpl
Alzheimer’s disease
dc.subject.enpl
antioxidants
dc.subject.enpl
β-amyloid anti-aggregation properties
dc.subject.enpl
cholinesterase inhibitors
dc.subject.enpl
inhibitors of β-secretase
dc.subject.enpl
inhibitors of monoamine oxidase A/B
dc.subject.enpl
multi-target-directed ligands
dc.subject.enpl
neuroprotective properties
dc.subtypepl
Article
dc.titlepl
Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer's disease
dc.title.journalpl
Current Medicinal Chemistry
dc.typepl
JournalArticle
dspace.entity.type
Publication

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