Synthesis and evaluation of novel amide amino-ß-lactam derivatives as cholesterol absorption inhibitors.
Bioorg Med Chem
; 23(10): 2353-9, 2015 May 15.
Article
en En
| MEDLINE
| ID: mdl-25882530
The ß-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-ß-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibitors. We synthesized six new amide ezetimibe analogs. All new compounds exhibited low toxicity in MDCKIIwt, hNPC1L1/MDCKII and HepG2 cell lines and showed significant inhibition of cholesterol uptake in hNPC1L1/MDCKII cells. In addition, we determined the activity of the three compounds to inhibit cholesterol absorption in vivo. Our results demonstrate that these compounds considerably reduce cholesterol concentrations in liver and small intestine of mice. Thus, our newly synthesized amide ezetimibe analogs are cholesterol absorption inhibitors in vitro and in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Azetidinas
/
Colesterol
/
Beta-Lactamas
/
Ezetimiba
/
Absorción Intestinal
/
Anticolesterolemiantes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Reino Unido