Department of Organic Chemistry, University of Vigo, Spain.
Curr Top Med Chem. 2012;12(8):895-919. doi: 10.2174/156802612800166729.
Effective as statin drugs or acids are inhibitors mevinic limiting enzyme in cholesterol biosynthesis, 3-hydroxy- 3-methyl-glutaryl coenzyme A-3-hydroxy-3-reductase (HMGR), an enzyme responsible for the reduction the double methyl-glutaryl coenzyme A. These compounds promoted the synthesis and evaluation of new inhibitors of HMGR, called HMGRIs. The high number of potential candidates need to create models of quantitative structure-activity relationship in order to guide the HMGRI (3-hydroxy-3-methyl-glutarylcoenzyme A inhibitor) synthesis. In this work, we revised different computational studies for a very large and heterogeneous series of HMGRIs. First, we revised QSAR studies with conceptual parameters how flexibility of rotation, probability of availability, etc; Next, using method of regression analysis; and QSAR studies in order to understand the essential structural requirement for binding with receptor. Next, we review 3D QSAR, CoMFA and CoMSIA with different compound to find out the structural requirements for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory activity.
尽管他汀类药物或酸抑制剂米伐他汀在胆固醇生物合成中是有效的,但是它们是 3-羟基-3-甲基戊二酰基辅酶 A-3-羟 3-还原酶(HMGR)的限速酶抑制剂,该酶负责减少双甲基戊二酰基辅酶 A。这些化合物促进了 HMGR 的新抑制剂的合成和评估,称为 HMGRIs。需要创建大量潜在候选物的定量构效关系模型,以指导 HMGRI(3-羟基-3-甲基戊二酰基辅酶 A 抑制剂)的合成。在这项工作中,我们修订了针对非常大且异构系列的 HMGRIs 的不同计算研究。首先,我们修订了 QSAR 研究,其中包括旋转的灵活性、可用性概率等概念参数;接下来,使用回归分析方法;和 QSAR 研究,以了解与受体结合的基本结构要求。接下来,我们回顾了 3D-QSAR、CoMFA 和 CoMSIA 与不同化合物的关系,以找出 3-羟基-3-甲基戊二酰基辅酶 A(HMGR)抑制活性的结构要求。