Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis
Braz. J. Pharm. Sci. (Online)
;
58: e20028, 2022. tab, graf
Artículo
en Inglés
| LILACS
| ID: biblio-1403695
ABSTRACT
Abstract Dyslipidemia is an abnormal lipid profile associated with many common diseases, including coronary heart disease and atherosclerosis. Cholesteryl ester transfer protein (CETP) is a hydrophobic plasma glycoprotein that is responsible for the transfer of cholesteryl ester from high-density lipoprotein athero-protective particles to pro-atherogenic very low-density lipoprotein and low-density lipoprotein particles. The requirement for new CETP inhibitors, which block this process has driven our current work. Here, the synthesis as well as the ligand-based and structure-based design of seven oxoacetamido-benzamides 9a-g with CETP inhibitory activity is described. An in vitro study demonstrated that most of these compounds have appreciable CETP inhibitory activity. Compound 9g showed the highest inhibitory activity against CETP with an IC50 of 0.96 µM. Glide docking data for compounds 9a-g and torcetrapib provide evidence that they are accommodated in the CETP active site where hydrophobic interactions drive ligand/CETP complex formation. Furthermore, compounds 9a-g match the features of known CETP active inhibitors, providing a rationale for their high docking scores against the CETP binding domain. Therefore, these oxoacetamido-benzamides show potential for use as novel CETP inhibitors
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Benzamidas
/
Dislipidemias
/
Proteínas de Transferencia de Ésteres de Colesterol
Idioma:
Inglés
Revista:
Braz. J. Pharm. Sci. (Online)
Asunto de la revista:
Farmacologia
/
Teraputica
/
Toxicologia
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
Jordania
Institución/País de afiliación:
Al-Zaytoonah University of Jordan/JO
Similares
MEDLINE
...
LILACS
LIS