QSAR & Complex Network Study of the HMGR Inhibitors Structural Diversity

Author(s): Isela Garcia, Yagamare Fall, Generosa Gomez.

Journal Name: Current Drug Metabolism

Volume 11 , Issue 4 , 2010


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

Keywords: QSAR, Complex network, Lipid-lowering agent, Cholesterol level, Atherosclerotic disease, Antiparasite drug, Trypanosoma cruzi, Chagas' disease, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, CoMSIA, COMFA, topological indices

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2010
Page: [307 - 314]
Pages: 8
DOI: 10.2174/138920010791514243
Price: $58

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