Molecular Docking and Structure Activity Relationship Studies of NSAIDs. What do they Reveal about IC50?

Title:Molecular Docking and Structure Activity Relationship Studies of NSAIDs. What do they Reveal about IC50?

Volume: 14 Issue: 8

Author(s): Chrysoula Mikra, Georgios Rossos, Sotirios K. Hadjikakou and Nikolaos Kourkoumelis*

Affiliation:

• Department of Medical Physics, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina,Greece

Keywords: NSAID, COX, molecular docking, QSAR, ADME, IC50, computational studies.

Abstract: Background: The cyclooxygenase (COX) enzymes are important biological targets for non-steroidal anti-inflammatory (NSAID) drugs because they can inhibit the prostaglandin synthesis during the inflammatory process. Although COX enzymes are structurally well characterized, accurate ligand docking studies are challenging due to their varied structural and chemical properties.

Methods: We conducted molecular docking studies of 30 structurally diverse NSAIDs using two different software packages in an effort to examine if a linear dependency between experimental IC50 values (50% binding inhibition) and binding energies is realistic for this class of compounds.

Results: Results showed that the docking technique can approximate the selectivity of NSAIDs via energetic terms but not the IC50. Evaluation of ADME parameters coupled with multiple linear regression was performed to create statistically significant QSAR models correlating IC50 values to physicochemical and biological parameters for the COX-2 enzyme.

Conclusion: The distribution of the electrostatic potential, nucleophilicity and electrophilicity was found to be the most important descriptor for drug-enzyme interactions.

Cite this article as:

Mikra Chrysoula, Rossos Georgios, Hadjikakou K. Sotirios and Kourkoumelis Nikolaos*, Molecular Docking and Structure Activity Relationship Studies of NSAIDs. What do they Reveal about IC50?, Letters in Drug Design & Discovery 2017; 14 (8) . https://dx.doi.org/10.2174/1570180814666161207143231

DOI https://dx.doi.org/10.2174/1570180814666161207143231	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X