Faculty of Pharmacy, Department of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Arch Pharm (Weinheim). 2017 Dec;350(12). doi: 10.1002/ardp.201700204. Epub 2017 Nov 7.
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 IC 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.
心血管疾病是发达国家最常见的死亡和发病原因；其风险与高密度脂蛋白（HDL）胆固醇水平呈负相关。因此，人们非常有兴趣开发新的胆固醇酯转移蛋白（CETP）抑制剂，以提高 HDL 作为预防心血管疾病的新方法。本文对旨在抑制 CETP 的十个苄基苯甲酰胺 8a-j 进行了合成和表征。体外 CETP 抑制生物测定显示，苯甲酰胺 8j 活性最佳，在 10μM 浓度下的抑制率为 82.2%，IC 值为 1.3μM。对接研究表明，验证的化合物适应 CETP 的结合裂隙，并被疏水性衬里包围。此外，8a-j 的支架与 CETP 抑制剂的药效团点相匹配，特别是在其疏水性和芳香性功能方面。
