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2000
Volume 13, Issue 3
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Background: Hyperlipidemia is one of the most common chronic diseases worldwide. Cholesteryl ester transfer protein (CETP) is a hydrophobic glycoprotein that facilitates the transfer of cholesteryl ester from the atheroprotective high-density lipoprotein (HDL) to the proatherogenic low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Methods: In this work, synthesis and characterization of five fluorinated 3-benzylamino benzamides 8a-8c, 13a and 13b that target CETP activity were carried out. Results: Benzamides 8b and 8a showed the highest CETP inhibitory activities with an IC50 of 0.75 μ M and 4.1 μ M respectively. It was found that the presence of p-OCF3 group (as in 8a-8c) enhances CETP inhibitory activity more than p-OCF2CHF2 (as in 13a and 13b) which could be attributed to the bulkiness of the tetrafluoroethoxy group hindering their proper orientation in the binding domain. Additionally m-F derivatives were found to have higher activity against CETP than p-F ones leaving the o-F analogues with the weakest anti-CETP bioactivity. Conclusion: Ligand-based and structure-based drug design strategies confirm that hydrophobic interaction mediates ligand/protein complex formation and explains the activity of our verified molecules.

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/content/journals/mc/10.2174/1573406412666161104121042
2017-05-01
2025-06-11
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