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Multifunctional Donepezil Analogues as Cholinesterase and BACE1 Inhibitors.
Green, Keith D; Fosso, Marina Y; Garneau-Tsodikova, Sylvie.
Afiliação
  • Green KD; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA. kgr234@uky.edu.
  • Fosso MY; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA. marina.fosso@uky.edu.
  • Garneau-Tsodikova S; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA. sylviegtsodikova@uky.edu.
Molecules ; 23(12)2018 Dec 08.
Article em En | MEDLINE | ID: mdl-30544832
A series of 22 donepezil analogues were synthesized through alkylation/benzylation and compared to donepezil and its 6-O-desmethyl adduct. All the compounds were found to be potent inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes responsible for the hydrolysis of the neurotransmitter acetylcholine in Alzheimer's disease patient brains. Many of them displayed lower inhibitory concentrations of EeAChE (IC50 = 0.016 ± 0.001 µM to 0.23 ± 0.03 µM) and EfBChE (IC50 = 0.11 ± 0.01 µM to 1.3 ± 0.2 µM) than donepezil. One of the better compounds was tested against HsAChE and was found to be even more active than donepezil and inhibited HsAChE better than EeAChE. The analogues with the aromatic substituents were generally more potent than the ones with aliphatic substituents. Five of the analogues also inhibited the action of ß-secretase (BACE1) enzyme.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores da Colinesterase / Ácido Aspártico Endopeptidases / Donepezila Limite: Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores da Colinesterase / Ácido Aspártico Endopeptidases / Donepezila Limite: Humans Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos