Combined QSAR Model and Chemical Similarity Search for Novel HMG-CoA Reductase Inhibitors for Coronary Heart Disease

Abstract

Background: Coronary heart disease generally occurs due to cholesterol accumulation in the walls of the heart arteries. Statins are the most widely used drugs which work by inhibiting the active site of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme that is responsible for cholesterol synthesis. Series of atorvasatin analogs with HMGCR inhibition activity have been synthesised experimentally which would be expensive and time consuming. Method: In the present study, we employed both the QSAR model and chemical similarity search for identifying novel HMGCR inhibitors for heart related diseases. To implement this, a 2D QSAR model was developed by correlating the structural properties to their biological activity of a series of atoravastatin analogs reported as HMGCR inhibitors. Then, the chemical similarity search of atorvastatin analogs was performed by using PubChem database search. Results: The three descriptor model of charge (GATS1p), connectivity (SCH-7) and distance (VE1_D) of the molecules is obtained for HMGCR inhibition with the statistical values of R2= 0.67, RMSEtr= 0.33, R2ext= 0.64 and CCCext= 0.76. The 109 novel compounds were obtained by chemical similarily search and the inhibition activities of the compounds were calculated using QSAR model, which were close in the range of experimentally observed threshold. Conclusion: The present study suggests that QSAR model and chemical similarity search could be used in combination for identification of novel compounds with activity by in silico with less computation and effort.

Biological Membrane-Penetrating Peptides: Computational Prediction and Applications

“…Quantitative structure-property relationships (QSPRs) are statistical methods based on regression data analyses that have been widely applied in Computational Chemistry to perform bioprospection and develop new bioactive compounds (Melo-Filho et al, 2016;Gomes et al, 2017;Rajathei et al, 2020;Tutumlu et al, 2020;Al-Attraqchi and Venugopala, 2021). The QSPR represents mathematical models that aim to create correlations between the biological property (e.g.…”

MOZART, a QSAR Multi-Target Web-Based Tool to Predict Multiple Drug–Enzyme Interactions

“…QSAR methodology has been used together with docking in the development of new drugs. QSAR has been widely used to predict drug activity against specific enzyme targets [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. However, the vast majority of these models are not implemented in a web server or a free-to-use software and cannot be easily used.…”