Ursolic acid ester derivatives designed as novel plant-based CETP inhibitors (Bioorg Med Chem Lett 2019)

Original title: Synthesis, biological evaluation and SAR studies of ursolic acid 3β-ester derivatives as novel CETP inhibitors

Bioorg Med Chem Lett · 17 November 2019 · 4

Chen C, Sun R, Sun Y, Chen X, Li F, Wen X, Yuan H, Chen D

Researchers synthesised a series of ursolic acid 3-beta-ester derivatives and evaluated their ability to inhibit cholesteryl ester transfer protein (CETP), an established target for lowering LDL cholesterol and raising HDL cholesterol. The most active compound, U12, inhibited CETP with an IC50 of 2.4 micromolar in an enzymatic assay. Molecular docking suggested that hydrogen-bond interactions between carboxyl groups at both ends of the compound and polar residues in the CETP active site, including Ser191, Cys13, and Ser230, significantly enhanced inhibitory activity. The study provides structural insight for further optimisation of pentacyclic triterpenoid derivatives as CETP inhibitors.

Original 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 3β-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 μM 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 3β-ester derivatives and CETP protein for the further modification and optimization.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.