3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2

Authors

  • Kulwinder Singh Department of Biotechnology, Punjabi University, Patiala - 147002, Punjab
  • Monika . Department of Biotechnology, Mata Gujri College, Fatehgarh Sahib - 140406, Punjab
  • Neelam Verma Department of Biotechnology, Punjabi University, Patiala - 147002, Punjab

Keywords:

QSAR, Multiple linear regression, Physicochemical descriptors, Docking, COX-2, Scigress explorer, Molegro virtual docker

Abstract

Background:Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design.

Methods:3-Dimensional QSAR studies were performed on a series of tetrasubstituted pyrazole derivatives by using Scigress Explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of COX-2 protein.

Results:The multiple linear regression analysis was used to correlate the physicochemical descriptors with the COX-2 inhibitory activity of 24 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.835. This model was further used to predict the COX-2 inhibitory activity of 10 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of COX-2 protein (PDB ID: 1CX2). Predicted pIC50 value of one of the test compounds was 7.048 and it showed H-bond interactions with His90 & Tyr355 residues.

Conclusion:The present study shall help in rational drug design and synthesis of new selective COX-2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between COX-2 and the novel tetrasubstituted pyrazole derivative compounds.

 

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Published

2017-01-23

How to Cite

Singh, K., ., M., & Verma, N. (2017). 3-Dimensional quantitative structure-activity relationship and molecular docking studies of tetrasubstituted pyrazole derivatives as inhibitors of cyclooxygenase-2. International Journal of Research in Medical Sciences, 2(2), 612–619. Retrieved from https://www.msjonline.org/index.php/ijrms/article/view/2208

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Original Research Articles