Title:CETP Inhibitory Activity of Chlorobenzyl Benzamides: QPLD Docking, Pharmacophore Mapping and Synthesis
VOLUME: 14 ISSUE: 12
Author(s):Reema Abu Khalaf*, Hamada Abd El-Aziz, Dima Sabbah, Ghadeer Albadawi and Ghassan Abu Sheikha
Affiliation:Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman
Keywords:Atherosclerosis, CETP inhibitors, chlorobenzyl benzamides, docking, QPLD, pharmacophore mapping.
Abstract:Background: Elevated levels of serum LDL and total cholesterol are considered important
risk factors for the development of atherosclerosis. Cholesteryl ester transfer protein inhibition
raises HDL levels and reduces atherosclerotic lesions.
Objective: Consequently, there is a great interest in developing new CETP inhibitors.
Methods: Herein, synthesis of four chlorobenzyl benzamides 8a-d that aim at CETP inhibition was
performed.
Results: Benzamide 8a showed the best CETP inhibitory activity with an IC50 of 1.6 µM. In vitro
biological data shows that the presence of p-trifluoromethoxy group enhances CETP inhibitory
activity more than m-trifluoromethyl groups. QPLD docking shows that the verified compounds
accommodate the binding cleft of CETP and are enclosed by hydrophobic lining. The scaffold of
8a-d matches the pharmacophoric points of CETP inhibitors; particularly hydrophobic and aromatic
functionalities.
Conclusion: Future structural modification is needed to improve CETP inhibitory activity and to
enhance understanding of the structure-activity relationship.
