Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.
Kazan (Volga Region) Federal University, 18 Kremlevskaya St., 420008 Kazan, Russian Federation.
Biochim Biophys Acta Biomembr. 2017 Mar;1859(3):295-300. doi: 10.1016/j.bbamem.2016.12.006. Epub 2016 Dec 16.
Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins reduce the amount of low-density lipoprotein (LDL) cholesterol, which is known as a well-established risk factor for atherosclerosis. Despite the fact that statins have a common pharmacologic target essential to sterol biosynthesis, their efficacy, safety, and potential non-LDL actions vary significantly for different statins. There is a hypothesis that pharmacological features of statins depend on their location in cell membrane, but to the present day there is a lack of information in literature on interactions of statins with the surface of the cell membrane in liquid media. The results of NMR experiments showed that all studied statins form intermolecular complexes with models of cell membranes (dodecylphosphocholine micelles) in water solution. Locations of pravastatin, simvastatin, fluvastatin and cerivastatin on model membranes were established by NOESY NMR data. Distinctions in their positions can explain differences in pharmacological properties of studied compounds.
羟甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂或他汀类药物可降低低密度脂蛋白（LDL）胆固醇的含量，已知 LDL 胆固醇是动脉粥样硬化的一个既定危险因素。尽管他汀类药物具有共同的、对固醇生物合成至关重要的药理学靶点，但不同的他汀类药物在疗效、安全性和潜在的非 LDL 作用方面存在显著差异。有一种假设认为，他汀类药物的药理学特征取决于它们在细胞膜中的位置，但迄今为止，关于他汀类药物与液体介质中细胞膜表面相互作用的文献信息仍然缺乏。NMR 实验结果表明，所有研究的他汀类药物在水溶液中均与细胞膜模型（十二烷基磷酸胆碱胶束）形成分子间复合物。通过 NOESY NMR 数据确定了普伐他汀、辛伐他汀、氟伐他汀和西立伐他汀在模型膜上的位置。它们位置的差异可以解释研究化合物药理学特性的差异。
