Objectives: To design novel 3,6-bis(3'- substituted propoxy) and 3,6-bis(5'- substituted pentyloxy)xanthone derivatives targeting Prostaglandin endoperoxide synthase-2 by molecular docking study and to evaluate their COX-2 inhibitory potential.
Materials and Method: The protein structure was downloaded from RCSB protein databank and the ligands were prepared using Chemdraw freeware. Discovery Studio version 2.5 was used for studying the binding interactions. Molinspiration Cheminformatics and OSIRIS property explorer were utilized online to predict the molecular properties and toxicities of the designed compounds.
Result: The in silico ligand binding interactions of compounds S3, S6, S14, S17 and S20 suggested approx. > 30% higher binding energy values than the standard Diclofenac (Binding energy -155.46 Kcal/mol). The binding energy was observed from -270.61 to -65.12 Kcal/mol. The rank of each designed compounds were determined on the basis of lowest energy score.
Conclusion: Molecular docking studies have shown significant anti-inflammatory activity in the synthesized 3,6-bis(3'- substituted propoxy) and 3,6-bis(5'- substituted pentyloxy)xanthone derivatives in comparision to the standard, Diclofenac. The incorporation of primary and secondary nitrogens in the chemical structure is found to favour the antiinflammatory potential of the designed compounds.