Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation / 药学学报
Acta Pharmaceutica Sinica
; (12): 1671-1676, 2013.
Article
en Zh
| WPRIM
| ID: wpr-298027
Biblioteca responsable:
WPRO
ABSTRACT
A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Farmacología
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Acetilcolinesterasa
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Sitios de Unión
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Butirilcolinesterasa
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Química
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Inhibidores de la Colinesterasa
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Péptidos beta-Amiloides
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Metabolismo
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Nicotina
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2013
Tipo del documento:
Article