Understanding the Dual Inhibition of COX-2 and Carbonic Anhydrase-II by Celecoxib and CG100649 Using Density Functional Theory Calculations and other Molecular Modelling Approaches

Title:Understanding the Dual Inhibition of COX-2 and Carbonic Anhydrase-II by Celecoxib and CG100649 Using Density Functional Theory Calculations and other Molecular Modelling Approaches

Volume: 22 Issue: 10

Author(s): Omkar Singh, Kumar R. Kakularam, Pallu Reddanna and Polamarasetty Aparoy

Affiliation:

Keywords: CA-II, COX-2, docking, HOMO, ligand based pharmacophore, LUMO, receptor based pharmacophore.

Abstract: Recent developments in the dual inhibition studies of cyclooxygenase-2 (COX-2) and carbonic anhydrase (CA-II) imply a promising platform for the development of new generations of nonsteroidal anti-inflammatory drugs (NSAIDs). CG100649 is such a molecule that got recently approved by Korean Ministry of Food and Drug safety (MFDS) and is being marketed by the name polmacoxib for the treatment of osteoarthritis. CG100649 significantly inhibits CA-II in blood and COX-2 in inflammatory tissues. However, the mechanism of CG100649 dual inhibition of COX-2/CA-II is not well understood. In this study, we employed well known methods like pharmacophore modelling, a DFT based quantum chemical descriptors analysis, and molecular docking to explore the chemical features and to understand the binding behaviour of CG100649 along with other COX-2/CA-II dual inhibitors. The HOMO-LUMO and docking results indicated the prominent role of aryl sulphonamide in CG100649. The aryl sulphonamide moiety formed T-shaped Π…Π interactions with His94 in the CA-II active site, which was not observed in the case of celecoxib. Other crucial interactions were also observed which may aid in further understanding the action of dual inhibitors of this class.

Cite this article as:

Singh Omkar, Kakularam R. Kumar, Reddanna Pallu and Aparoy Polamarasetty, Understanding the Dual Inhibition of COX-2 and Carbonic Anhydrase-II by Celecoxib and CG100649 Using Density Functional Theory Calculations and other Molecular Modelling Approaches, Protein & Peptide Letters 2015; 22 (10) . https://dx.doi.org/10.2174/0929866522666150622102131

DOI https://dx.doi.org/10.2174/0929866522666150622102131	Print ISSN 0929-8665
Publisher Name Bentham Science Publisher	Online ISSN 1875-5305