Current Computer-Aided Drug DesignCurrent Computer-Aided Drug DesignCurrent Computer-Aided Drug Design1573-40991875-6697Bentham Science64414910.2174/1573409919666230509123852ChemistryResearch ArticleSynthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP InhibitorsAbu KhalafReemainfo@benthamscience.netAbusaadAmaniinfo@benthamscience.netAl-NawaisehBara'ainfo@benthamscience.netSabbahDimainfo@benthamscience.netAlbadawiGhadeerinfo@benthamscience.netDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of JordanDepartment of Pharmacy, Al-Zaytoonah University of Jordan0105202420556457407012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjeid.com/1573-4099/article/view/644149

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.

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