title: QSAR & complex network study of the HMGR inhibitors structural diversity.
abstract: Efficient drugs such as statins or mevinic acids are inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), an enzyme responsible for the double reduction of 3-hydroxy-3-methyl-glutaryl coenzyme A. These compounds promoted the synthesis and evaluation of new inhibitors for HMGR, named HMGRIs. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the HMGRI (3-hydroxy-3-methyl-glutaryl coenzyme 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 such as flexibility of rotation, probability of availability, etc; we then used the method of regression analysis; and QSAR studies in order to understand the essential structural requirement for binding with receptor. Next, we reviewed 3D QSAR, CoMFA and CoMSIA with different compounds to find out the structural requirements for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitory activity.
authors.affiliation: Department of Organic Chemistry, University of Vigo, Spain. iselapintos@yahoo.es
authors.forename: Isela
authors.initials: I
authors.lastname: García
authors.forename: Yagamare Fall
authors.initials: YF
authors.lastname: Diop
authors.forename: Generosa
authors.initials: G
authors.lastname: Gómez
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006903:Hydroxymethylglutaryl CoA Reductases