Potential Naproxen derivatives as Selective COX-2 inhibitors: Design, ADME, Docking, and Molecular Dynamics Simulations.

Year 2026, Volume: 10 Issue: 3, 24 - 38

Noor Riyadh , Ayad Kareem , Mohammed Dheyaa Hamdi

Abstract

Seven new Naproxen derivatives featuring a 2-azetidinone ring were designed to assess their potential efficacy against COX2. Molecular docking was performed using the crystalline structure of COX2, with meloxicam as a control for comparison (PDB ID: 4M11), utilizing GOLD software. In silico ADME studies were subsequently carried out via the Swiss ADME website. Molecular dynamics simulations of compound Nr1 complexed with COX2 were conducted using the Schrödinger Suite. Results indicated the best binding energy within the receptor pocket, suggesting promising activity against the COX2 protein receptor. Compounds Nr1 and Nr2 exhibited the highest PLP fitness levels for the anti-inflammatory protein (87.784 and 82.212, respectively, on average). All compounds complied with Lipinski's Rule and demonstrated high gastrointestinal absorption. Molecular dynamics results revealed that compound Nr7 showed optimal alignment with the COX2 receptor. These findings highlight a promising avenue for developing effective treatments.

Keywords

Cyclooxygenase-2 , Naproxen derivatives , Swiss ADME , Molecular dynamic stimulation

Ethical Statement

This research is based on previously published data and does not involve human or animal subjects requiring ethical approval.

Supporting Institution

Department of Pharmaceutical Chemistry at the College of Pharmacy/Mustansiriyah University (www.uomustansiriyah.edu.iq) Baghdad, Iraq.

Thanks

I would like to express my gratitude to all colleagues and researchers whose work contributed to this study. Special thanks to and Department of Pharmaceutical Chemistry at the College of Pharmacy/Mustansiriyah University (www.uomustansiriyah.edu.iq) Baghdad, Iraq, for their assistance with this project.

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