Synthesis, biological evaluation and SAR studies of ursolic acid 3ß-ester derivatives as novel CETP inhibitors.
Bioorg Med Chem Lett
; 30(2): 126824, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31780304
ABSTRACT
Cholesteryl ester transfer protein (CETP) is an attractive therapeutic target for the prevention and treatment of cardiovascular diseases by lowering low-density lipoprotein cholesterol levels as well as raising high-density lipoprotein cholesterol levels in human plasma. Herein, a series of ursolic acid 3ß-ester derivatives were designed, synthesized and evaluated for the CETP inhibiting activities. Among these compounds, the most active compound is U12 with an IC50 value of 2.4⯵M in enzymatic assay. The docking studies showed that the possible hydrogen bond interactions between the carboxyl groups at both ends of the molecule skeleton and several polar residues (such as Ser191, Cys13 and Ser230) in the active site region of CETP could significantly enhance the inhibition activity. This study provides structural insight of the interactions between these pentacyclic triterpenoid 3ß-ester derivatives and CETP protein for the further modification and optimization.
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Base de dados:
MEDLINE
Assunto principal:
Ésteres
/
Proteínas de Transferência de Ésteres de Colesterol
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Simulação de Acoplamento Molecular
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article