Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis
Título del documento: Cholesteryl ester transfer protein inhibitory oxoacetamido-benzamide derivatives: Glide docking, pharmacophore mapping, and synthesis
Revista: Brazilian Journal of Pharmaceutical Sciences
Base de datos: PERIÓDICA
Número de sistema: 000451780
ISSN: 1984-8250
Autores: 1
1
1
1
Instituciones: 1Al-Zaytoonah University of Jordan, Faculty of Pharmacy, Ammán. Jordania
Año:
Volumen: 58
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés 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
Disciplinas: Química,
Medicina
Palabras clave: Metabolismo y nutrición,
Farmacología,
Dislipidemia,
Glucoproteínas séricas,
Proteína de transferencia de esteres de colesterol,
Acoplamiento deslizante,
Farmacóforos
Keyword: Metabolism and nutrition,
Pharmacology,
Dyslipidemia,
Serum glycoproteins,
Cholesteryl ester transfer protein,
Glide docking,
Pharmacophores
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