Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors

Reema Abu Khalaf; Amani Abusaad; Bara'a Al-Nawaiseh; Dima Sabbah; Ghadeer Albadawi

doi:10.2174/1573409919666230509123852

Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors

Curr Comput Aided Drug Des. 2023 May 9. doi: 10.2174/1573409919666230509123852. Online ahead of print.

Authors

Reema Abu Khalaf¹, Amani Abusaad¹, Bara'a Al-Nawaiseh¹, Dima Sabbah¹, Ghadeer Albadawi¹

Affiliation

¹ Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

PMID: 37165488
DOI: 10.2174/1573409919666230509123852

Abstract

Background: Hyperlipidemia is considered a major risk factor for the progress of atherosclerosis.

Objective: Cholesteryl ester transfer protein (CETP) facilitates the relocation of cholesterol esters from HDL to LDL. CETP inhibition produces higher HDL and lower LDL levels.

Methods: Synthesis of nine benzylamino benzamides 8a-8f and 9a-9c was performed.

Results: In vitro biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC50 of 1.03 µM. Induced-fit docking demonstrated that 8a-8f and 9a-9c accommodated the CETP active site and hydrophobic interaction predominated ligand/ CETP complex formation.

Conclusion: Pharmacophore mapping showed that this scaffold endorsed CETP inhibitors features and consequently elaborated the high CETP binding affinity.

Keywords: CETP inhibitors; Hyperlipidemia; Induced-fit docking; Pharmacophore mapping; Trifluoromethyl benzamides.