Synthesis, Biological Evaluation, and Molecular Modeling Study of Substituted Benzyl Benzamides as CETP Inhibitors
| Autor: | Samar Bishtawi, Reema Abu Khalaf, Ghadeer Albadawi, Dima A. Sabbah, Eveen Al-Shalabi, Ghassan Abu Sheikha |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
biology Molecular model Cholesterol Pharmaceutical Science 030204 cardiovascular system & hematology In vitro carbohydrates (lipids) 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine chemistry Biochemistry Docking (molecular) Drug Discovery Cholesterylester transfer protein biology.protein lipids (amino acids peptides and proteins) Benzamide IC50 Lipoprotein |
| Zdroj: | Archiv der Pharmazie. 350:1700204 |
| ISSN: | 0365-6233 |
| DOI: | 10.1002/ardp.201700204 |
| Popis: | Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high-density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a-j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82.2% at 10 μM concentration and an IC50 value of 1.3 μM. The docking study shows that the verified compounds accommodate the binding cleft of CETP and are enclosed by a hydrophobic lining. Furthermore, the scaffold of 8a-j matches the pharmacophoric points of CETP inhibitors, particularly in its hydrophobic and aromatic functionalities. |
| Databáze: | OpenAIRE |
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