Virtual ligand screening of α-glucosidase: Identification of a novel potent noncarbohydrate mimetic inhibitor.
Bioorg Med Chem Lett
; 22(1): 62-4, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22154663
5-Thiazoleacetamide derivatives of AR122 and AR125 were screened as α-glucosidase inhibitors by in silico high-throughput screening from commercial drug-like small compound libraries. Inhibition of α-glucosidase with AR122 and AR125 is time dependent: with no preincubation, AR122 and AR125 are relatively moderate inhibitors, but interestingly, after a 120 min incubation, they were 50-fold more potent (AR122: IC(50)=2.47 µM and AR125: IC(50)=27.1 µM). Plots of ln [residual α-glucosidase activity %] versus preincubation time show a pseudo-first order kinetics for both inhibitors. Through dialysis of enzyme-inhibitor complexes, no activity recovery was shown. These results suggest that AR122 and AR125 constitute a new class of noncarbohydrate mimetic inhibitor with an irreversible mechanism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Química Farmacêutica
/
Inibidores Enzimáticos
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Alfa-Glucosidases
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article