New 4-N-phenylaminoquinoline derivatives as antioxidant, metal chelating and cholinesterase inhibitors for Alzheimer's disease.
Bioorg Chem
; 93: 103328, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31600664
ABSTRACT
A series of new 4-N-phenylaminoquinoline derivatives were designed, synthesized, and their anticholinesterase activities, 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, metal-chelating ability were tested. Among them, compounds 11j, 11k and 11l had comparable inhibition activities to reference drug galantamine both in AChE and in BChE. Especially, compound 11j revealed the most potent inhibition to eeAChE and eqBChE with IC50 values of 1.20⯵M and 18.52⯵M, respectively. Furthermore, both kinetic analysis of AChE inhibition and molecular docking study indicated that compound 11j was mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE, and propidium iodide displacement assay showed significant displacement of propidium iodide with compound 11k (25.80%) from PAS of eeAChE. More importantly, compound 11l displayed excellent DPPH radical scavenging activity (84% at 1â¯mg/mL), and its EC50 value was 0.328⯵M. In addition, compounds 11a, 11j, 11k and 11l exhibited obvious biometal chelating abilities toward Al3+, Fe2+, Cu2+ and Zn2+ ions. Taken together, 4-N-phenylaminoquinoline derivatives targeting multiple pathogenetic factors deserve further investigation for treatment of AD.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quelantes
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Inhibidores de la Colinesterasa
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Enfermedad de Alzheimer
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Aminoquinolinas
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Metales
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Antioxidantes
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article