The Search for Cyclooxygenase-2 (COX-2) Inhibitors for the Treatment of Inflammation Disease: An in-silico Study

Abstract

Ruslin Ruslin,1 Yamin Yamin,1 Henny Kasmawati,1 Samuel Mangrura,2 Laode Kadidae,2 Armid Alroem,2 Muhammad Arba1 1Faculty of Pharmacy, Universitas Halu Oleo, Kendari, 93232, Indonesia; 2Department of Chemistry, Faculty of Mathematics and Natural; Sciences, Universitas Halu Oleo, Kendari, 93232, IndonesiaCorrespondence: Ruslin Ruslin, Email [email protected]: Cyclooxygenase (COX-2) has been validated as a molecular target for treating inflammatory diseases. The present work was performed to identify potential COX-2 inhibitors by employing pharmacophore modeling.Methods: The pharmacophore features consisted of seven features, ie, three hydrophobic, one negative ion, and three hydrogen bond acceptors, which were developed based on the structure of COX-2 inhibitor, (R)-naproxen.Results: The pharmacophore model was validated with a Goodness of Hit (GH score) of 0.754 and the values of AUC100% 0.51. Screening against the ZINC database retrieved 1675 hits, while the molecular docking procedure identified four best hit molecules in term of binding orientation and binding energies, ie, Lig_1805/ZINC103584272 (E = − 11.03 kcal/mol), Lig_553/ZINC408573132 (E = − 10.92 kcal/mol), Lig_680/ZINC103584263 (E = − 10.90 kcal/mol), and Lig_2006/ZINC19324645 (E = − 10.62 kcal/mol).Conclusion: The interactions of the four hits occurred in the binding site as (R)-naproxen did, and interestingly, their binding affinities were stronger than (R)-naproxen, implying their potential as COX-2 inhibitors.Keywords: COX-2 inhibitor, inflammation disease, molecular docking, pharmacophore modeling, ZINC database

Keywords

• cox-2 inhibitor
• inflammation disease
• molecular docking
• pharmacophore modeling
• zinc database