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Current Computer-Aided Drug Design

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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

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

Author(s): Reema Abu Khalaf*, Amani Abusaad, Bara'a Al-Nawaiseh, Dima Sabbah and Ghadeer Albadawi

Volume 20, Issue 5, 2024

Published on: 18 May, 2023

Page: [564 - 574] Pages: 11

DOI: 10.2174/1573409919666230509123852

Price: $65

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, molecular docking.

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Graphical Abstract

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