In Silico Molecular Docking of Xanthone Derivatives as Cyclooxygenase-2 Inhibitor Agents

Abstract

Objective: To demonstrate the potential ofdifferent xanthone derivatives as cyclooxygenase-2 (COX-2) inhibitor agents and their selectivity against cycloooxygenase-1 (COX-1) and COX-2 using molecular simulation. Methods:Nine novel xanthone derivatives (compounds A-I) were employed to dock against protein COX-2 (Protein Data Bank/PDB ID: 1CX2) and COX-1 (PDB ID: 3N8Z). Celecoxib, a selective COX-2 inhibitor, was chosen as a control compound. The free binding energy produced by the docking was scored using Protein-Ligand Ant System (PLANTS) and the hydrogen bonds (H-bonds) between ligands and enzymes were visualised using Pymol.Results: Molecular docking studies revealed that celecoxib docked to the active site of COX-2 enzyme, but not to COX-1; where as xanthone derivatives docked to the active site of both COX-2 and COX-1. Free binding energy of xanthone derivatives ranged between-73, 57 to-79,18 and between-73,06 to-79,25 against COX-2 and COX-1, respectively, and-78,13 against celecoxib. H-bonds in the molecule of xanthone derivatives and COX-2 protein were found in amino acid residues Arg 120 , Tyr 355 , Tyr 385 , and Ser 353 . There was an insignificant difference between the free binding energyof xanthone derivatives against COX-2 and against COX-1, suggesting that their inhibition was non-selective. Conclusion:In conclusion, in silico studies showed that xanthone derivatives could be effective as potential inhibitors against COX-2, although they are not selective.

The Biophysical Characteristics and Structural Exploration of Programmed Cell Death Regulator B-Cell Lymphoma 2-Associated X Protein of Chinese Liver Fluke (Clonorchis Sinensis)

“…For the translocation of BAX to mitochondria, a mitochondrial addressing signal of N-terminal Hα1 is believed to be necessary [29]. Recent bioinformatical research methods were very helpful for the discovery process of new biologically and biomedically important protein molecules [30][31][32][33][34][35][36][37][38][39]. Therefore, varied structural forms of BAX molecules in the different organisms (e.g., Chinese liver fluke) must be identified for bio-medical interventions.…”

DFT Calculations and In Silico Studies on the Schiff base derivatives with Antibacterial Activities

“…6) and the binding energy values are noted in Table 4. The compound 1 shows two π-π interaction, first one was formed between the 3,4-dimethoxybenzene ring and LEU 189 (bond length: 3.5 Å) and second one was formed between another 3,4-dimethoxybenzene ring and HIS 244 (bond length: Moreover, the binding model was enhanced by electrostatic interaction formed between compound 1 and residues CYS 112, PHE 304, GLU 302, HIS 244, and ILE 251, and Van der Waals interaction formed between compound 1 and residues LEU 205, THR 281, LEU 191, THR 190, ALA 111, LEU 189, GLY 306, ALA 303, LEU 220, PRO 243, THR 254, ILE 250, ASN 247, ALA 246, ASN 274, and LEU 142 of beta-ketoacyl-acp synthase III receptor [28][29][30].…”

Pharmacophore Screening and Molecular Docking of Phytoconstituents in Polygonum Sagittatum for Cyclooxygenase-2 Inhibitors Discovery.

“…Moreover, recent in silico study on xanthone derivatives resulted in the HB formation of the compounds with amino acid residues Arg120, Tyr355, Tyr385, and Ser353 [24].…”