Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile.
Bioorg Med Chem Lett
; 26(16): 4092-4, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27377327
ABSTRACT
We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46-2.1µM (for AChE) and 0.59-8.1µM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22-326mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
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Brometo de Piridostigmina
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Piridoxina
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Butirilcolinesterase
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Inibidores da Colinesterase
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article