Hypercholesterolemia is a serious condition that may lead to coronary heart disease, heart attack and stroke raising the rate of morbidity and mortality in hypocholesterolemic patients. Statins are one of the largest selling drugs for hypercholesterolemia. They serve as potential competitive inhibitors of HMG-CoA reductase that catalyzes the rate-limiting step of cholesterol biosynthesis cascade. They can be broadly classified into fermentation-derived, semisynthetic and synthetic statins. For the current study, synthetic statins like fluvastatin, cerivastatin, rosuvastatin were subjected to in silico analysis for their competitive binding with HMG-CoA reductase through molecular docking. The molecular interaction between HMG-CoA reductase with statins and their ADMET properties were studied using Maestro suite of Schrödinger software. The results of molecular docking depicted that fluvastatin had the highest docking score while that of rosuvastatin was the least. The prediction of pharmacokinetics of drug performed by QikProp also pointed the efficacy of fluvastatin as a potent inhibitor for HMG-CoA reductase enabling it to be an effective drug to treat hypercholesterolemia among the three synthetic statins.

中文翻译：

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合成他汀类药物对HMG-CoA还原酶抑制活性的分子对接和ADMET分析

高胆固醇血症是一种严重疾病，可能导致冠心病，心脏病发作和中风，从而降低低胆固醇血症患者的发病率和死亡率。他汀类药物是治疗高胆固醇血症的最大药物之一。它们是HMG-CoA还原酶的潜在竞争性抑制剂，可催化胆固醇生物合成级联的限速步骤。它们可以大致分为发酵来源的，半合成的和合成的他汀类。在本研究中，对氟伐他汀，西立伐他汀，瑞舒伐他汀等合成他汀类药物进行了计算机分析通过分子对接分析它们与HMG-CoA还原酶的竞争结合。使用Schrödinger软件的Maestro套件研究了HMG-CoA还原酶与他汀类药物之间的分子相互作用及其ADMET性质。分子对接的结果表明，氟伐他汀的对接得分最高，而瑞舒伐他汀的对接得分最低。QikProp对药物的药代动力学的预测也指出了氟伐他汀作为HMG-CoA还原酶的有效抑制剂的功效，使其成为治疗三种合成他汀类药物中高胆固醇血症的有效药物。