Fluorinated Benzyloxalamides: Glide Docking Pharmacophore Mapping Synthesis and In Vitro Evaluation as Potential Cholesteryl Ester Transfer Protein Inhibitors

Abstract

Abu Khalaf et al.: Fluorinated Benzyloxalamides as Cholesteryl Ester Transfer Protein InhibitorsWorldwide, cardiovascular disease is considered a major cause of death and disability. Age, sex, blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking and diabetes contribute in the development of the disease. Hence, high-density lipoprotein cholesterol modulation using cholesteryl ester transfer protein inhibitors could have a great role in reducing cardiovascular disease risk and mortality. In this work, ten new benzyloxalamides 8a-j were synthesized and characterized targeting the cholesteryl ester transfer protein inhibition. Biological study results showed that compound 8f had the greatest activity with a percentage inhibition of 64.1 at a concentration of 10 µM and an half-maximal inhibitory concentration of 2.1 µM. Functional moieties of 8a-j matched the cholesteryl ester transfer protein inhibitors pharmacophoric features; mainly the aromatic and hydrophobic ones. Moreover, Glide docking revealed that the targeted compounds lodge the binding site of cholesteryl ester transfer protein and are surrounded by hydrophobic liner. Benzyloxalamides can serve as lead scaffold for the development of cholesteryl ester transfer protein inhibitors.