QSAR & complex network study of the HMGR inhibitors structural diversity

• Published in: Current drug metabolism Vol. 11; no. 4; p. 307
• Main Authors: García, Isela, Diop, Yagamare Fall, Gómez, Generosa
• Format: Journal Article
• Language: English
• Published: Netherlands 01.05.2010
• Subjects: Animals; Drug Design; Humans; Hydroxymethylglutaryl CoA Reductases - drug effects; Hydroxymethylglutaryl CoA Reductases - metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemical synthesis; Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemistry; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Models, Molecular; Quantitative Structure-Activity Relationship; Regression Analysis
• ISSN: 1875-5453
• DOI: 10.2174/138920010791514243

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.