IN SILICO MOLECULAR DOCKING OF XANTHONE DERIVATIVES AS CYCLOOXYGENASE-2 INHIBITOR AGENTS


Isnatin Miladiyah, Jumina Jumina, Sofia Mubarika Haryana, Mustofa Mustofa

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; whereasxanthone 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 Arg120, Tyr355, Tyr385,and Ser353. 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.


Keywords


Xanthones, Molecular docking, Anticancer, COX-2, Selectivity

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About this article

Title

IN SILICO MOLECULAR DOCKING OF XANTHONE DERIVATIVES AS CYCLOOXYGENASE-2 INHIBITOR AGENTS

Keywords

Xanthones, Molecular docking, Anticancer, COX-2, Selectivity

DOI

10.22159/ijpps.2017v9i3.15382

Date

03-02-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 3, 2017 Page: 98-104

Online ISSN

0975-1491

Statistics

166 Views | 273 Downloads

Authors & Affiliations

Isnatin Miladiyah
Pharmacology Department, Faculty of Medicine, Islamic University of Indonesia, Yogyakarta
Indonesia

Jumina Jumina
Chemistry Department, Faculty of Mathematics and Natural Sciences, GadjahMada University, Yogyakarta

Sofia Mubarika Haryana
Histology and Cell Biology Department, Faculty of Medicine, GadjahMada University, Yogyakarta

Mustofa Mustofa
Pharmacology and Therapeutic Department, Faculty of Medicine, Gadjah Mada University, Yogyakarta


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