Dual-target compounds for Alzheimer's disease: Natural and synthetic AChE and BACE-1 dual-inhibitors and their structure-activity relationship (SAR).
Eur J Med Chem
; 221: 113492, 2021 Oct 05.
Article
em En
| MEDLINE
| ID: mdl-33984802
ABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative disease and represents the major cause of dementia worldwide. Currently, there are no available treatments capable to deliver disease-modifying effects, and the available drugs can only alleviate the symptoms. The exact pathology of AD is not yet fully understood and several hallmarks such as the presence of amyloid-ß (Aß) senile plaques, neurofibrillary tangles (NFTs) as well as the loss of cholinergic function have been associated to AD. Distinct pharmacological targets have been validated to address AD, with acetylcholinesterase (AChE) and ß-secretase-1 (BACE-1) being two of the most explored ones. A great deal of research has been devoted to the development of new AChE and BACE-1 effective inhibitors, tackled separately or in combination of both. The multi-factorial nature of AD conducted to the development of multi-target directed ligands (MTDLs), defined as single molecules capable to modulate more than one biological target, as an alternative approach to the old paradigm one-target one-drug. In this context, this review describes a collection of natural and synthetic compounds with dual-inhibitory properties towards both AChE and BACE-1 in the MTDLs context. Furthermore, this review also provides a critical comprehensive analysis of structure-activity relationships (SAR) of the synthetic compounds.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
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Produtos Biológicos
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Inibidores da Colinesterase
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Ácido Aspártico Endopeptidases
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Fármacos Neuroprotetores
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Portugal
País de publicação:
FR
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FRANCE
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FRANCIA
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FRANÇA