Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies.
Eur J Med Chem
; 46(6): 2011-21, 2011 Jun.
Article
en En
| MEDLINE
| ID: mdl-21439694
ABSTRACT
Naturally occurring pentacyclic triterpenes (PT), a novel class of inhibitors against glycogen phosphorylase (GP), hold promise for the treatment of type-2 diabetes and other diseases with disorders in glycogen metabolism. To identify novel and more potent GP inhibitors, the receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) approaches were performed to investigate the quantitative structure-activity relationships (QSAR) among 106 PT analogues. The validated models demonstrated that the elongated or bulky substitutions in C17 position and/or C2, C3 positions are favorable. Then based on the structural information extracted from these models, 56 derivatives were synthesized and biochemically tested in this study. The IC50 value of the most potent compound P50 was found to be 1.1 µM.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Relación Estructura-Actividad Cuantitativa
/
Glucógeno Fosforilasa de Forma Muscular
/
Inhibidores Enzimáticos
/
Triterpenos Pentacíclicos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2011
Tipo del documento:
Article
País de afiliación:
China