新型三氟甲基苯甲酰胺类 CETP 抑制剂的合成、分子模拟及生物评价。
Synthesis, Molecular Modeling and Biological Evaluation of Novel Trifluoromethyl Benzamides as Promising CETP Inhibitors.
机构信息
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
出版信息
Curr Comput Aided Drug Des. 2024;20(5):564-574. doi: 10.2174/1573409919666230509123852.
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
biological study displayed potential CETP inhibitory activity, where compound 9c had the best activity with an IC 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.
背景
高血脂被认为是动脉粥样硬化进展的一个主要危险因素。
目的
胆固醇酯转移蛋白（CETP）促进胆固醇酯从高密度脂蛋白（HDL）向低密度脂蛋白（LDL）的转移。CETP 抑制可产生更高的 HDL 和更低的 LDL 水平。
方法
合成了 9 个苄氨基苯甲酰胺 8a-8f 和 9a-9c。
结果
生物学研究显示出潜在的 CETP 抑制活性，其中化合物 9c 的活性最好，IC 为 1.03 μM。诱导契合对接表明，8a-8f 和 9a-9c 容纳了 CETP 的活性位点，并且疏水相互作用在配体/CETP 复合物的形成中占主导地位。
结论
药效团映射表明，该支架支持 CETP 抑制剂的特征，从而提高了 CETP 的结合亲和力。
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