Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates.
J Enzyme Inhib Med Chem
; 33(1): 1212-1224, 2018 Dec.
Article
en En
| MEDLINE
| ID: mdl-30160188
ABSTRACT
A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer's disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aß) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0-30.0 µΜ) and moderate ability for inhibition of Aß1-42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aß42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aß1-42 induced toxicity. Structure-activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Piperidinas
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Inhibidores de la Colinesterasa
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Péptidos beta-Amiloides
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Enfermedad de Alzheimer
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Indanos
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Antioxidantes
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article