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


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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.

About the authors

Reema Abu Khalaf

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan

Author for correspondence.
Email: info@benthamscience.net

Amani Abusaad

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan

Email: info@benthamscience.net

Bara'a Al-Nawaiseh

Department of Pharmacy, Al-Zaytoonah University of Jordan

Email: info@benthamscience.net

Dima Sabbah

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan

Email: info@benthamscience.net

Ghadeer Albadawi

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan

Email: info@benthamscience.net

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