New series of monoquaternary pyridinium oximes: Synthesis and reactivation potency for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase.
Bioorg Med Chem Lett
; 19(17): 5101-4, 2009 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-19640713
ABSTRACT
The preparation of a series of monoquaternary pyridinium oximes bearing either a heterocyclic side chain or a functionalized aliphatic side chain and the corresponding in vitro evaluation for reactivation of paraoxon-inhibited electric eel acetylcholinesterase (EeAChE) and recombinant human acetylcholinesterase (rHuAChE) are reported. Several newly synthesized compounds efficiently reactivated inhibited EeAChE, but were poor reactivators of inhibited rHuAChE. Compounds bearing a thiophene ring in the side chain (20, 23, 26 and 29) showed better reactivation (24-37% for EeAChE and 5-9% for rHuAChE) compared to compounds with furan and isoxazole heterocycles (0-8% for EeAChE and 2-3% for rHuAChE) at 10(-5)M. The N-pyridyl-CH(2)COOH analog 8 reactivated EeAChE (36%) and rHuAChE (15%) at 10(-4)M with a k(r) value better than 2-pyridine aldoxime methiodide (2-PAM) for rHuAChE.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oximas
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Compostos de Pralidoxima
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Acetilcolinesterase
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Reativadores da Colinesterase
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article