Design, Molecular Docking Study and Synthesis of 3,6-Bis(3'-substituted propoxy)xanthone Derivatives as COX-2 Inhibitors

Abstract

New drug discovery is considered broadly in terms of two kinds of investigational activities such as exploration and exploitation. Docking of small molecules in the receptor binding site and estimation of binding affinity of the complex is a vital part of structure based drug design. The current study deals with the evaluation of cyclooxygenase (COX) inhibitory activity of xanthone using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. Molecular properties of the ligands were investigated by using Discovery Studio 3.1. The docking results showed that all the selected xanthone derivatives having binding energy ranging between -6.61 to -15.46 kcal/mol when compared with that of the standard drug i.e. celecoxib (-9.94 kcal/mol). All the 3,6-bis(3’-substituted propoxy)xanthone derivatives contributed cyclooxygenase inhibitory activity because of its structural parameters. Molecular docking analysis of these compounds can lead to further development of potent cyclooxygenase inhibitors for the treatment of inflammation. A further structure-based research methodology of virtual screening was employed to analyze the selectivity of the 2 isozymes. After docking study these derivatives were successfully synthesized.