Synthesis and structure-activity relationship of 13-hexylberberine analogues as CD36 antagonists / 药学学报
Acta Pharmaceutica Sinica
; (12): 1128-1133, 2010.
Article
en Zh
| WPRIM
| ID: wpr-353411
Biblioteca responsable:
WPRO
ABSTRACT
Scavenger receptor CD36 could bind and endocytose oxLDL into macrophages which were then differentiated into foam cells that constitute the atherosclerotic lesion core, and was considered to be a potential target to treat atherosclerosis. In the establishment of the compound library of berberine (BBR, 1) analogues, we discovered that 13-hexylberberine (2) showed an antagonistic activity against CD36. Taking 2 as the lead compound, 21 derivatives were synthesized and their antagonistic activities were evaluated via an ELISA-like high-throughput screening (HTS) model. The primary structure-activity relationships were studied. It was indicated that the introduction of suitable groups at the 2- and 3-position of the aromatic ring A or at the 9-position of the aromatic ring D could enhance the activity. Among the 21 studied compounds, 7g bearing a benzyloxyl group at the 9-position provided a highest CD36 antagonistic activity with the IC50 value of 7.7 micromol L(-1). Besides, its antagonistic activity was further verified with Sf9 insect cell HTS model. So berberine analogues are a new family of CD36 receptor antagonists and worthy to be studied further.
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Farmacología
/
Relación Estructura-Actividad
/
Virología
/
Berberina
/
Ensayo de Inmunoadsorción Enzimática
/
Línea Celular
/
Supervivencia Celular
/
Química
/
Spodoptera
/
Antígenos CD36
Límite:
Animals
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2010
Tipo del documento:
Article
Pais de publicación:
CHINA
/
CN
/
REPUBLIC OF CHINA