Khaleel, R. (2026). In Silico Design and SAR Studies Evaluation of New Amide Compounds as COX-1 and 2 Inhibitors. , 23(2), 79-88. doi: 10.33899/iraqij.p.2026.169794.1193
Radwan A.S. Khaleel. "In Silico Design and SAR Studies Evaluation of New Amide Compounds as COX-1 and 2 Inhibitors". , 23, 2, 2026, 79-88. doi: 10.33899/iraqij.p.2026.169794.1193
Khaleel, R. (2026). 'In Silico Design and SAR Studies Evaluation of New Amide Compounds as COX-1 and 2 Inhibitors', , 23(2), pp. 79-88. doi: 10.33899/iraqij.p.2026.169794.1193
Khaleel, R. In Silico Design and SAR Studies Evaluation of New Amide Compounds as COX-1 and 2 Inhibitors. , 2026; 23(2): 79-88. doi: 10.33899/iraqij.p.2026.169794.1193

In Silico Design and SAR Studies Evaluation of New Amide Compounds as COX-1 and 2 Inhibitors

Iraqi Journal of Pharmacy
Article 5, Volume 23, Issue 2, June 2026, Pages 79-88    PDF (966.98 K)
Document Type: Research Paper
DOI: 10.33899/iraqij.p.2026.169794.1193
Author
Radwan A.S. Khaleel*
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, Iraq
Abstract
Background: The Nonsteroidal anti-inflammatory drugs still are indispensable in the treatment of pain and inflammation, but the available agents have limitations due to their gastrointestinal toxicity or cardiovascular risk. In this study, molecular docking was used to screen for new amide-based COX inhibitors that demonstrated an improved selectivity profile. Methods: A series of 132 amide derivatives of four molecular scaffolds (ortho-, meta-, para-aminobenzoic acid, and para-phenylenediamine) was designed and docked to COX-1 and COX-2 enzymes. Binding energies, selectivity indices and pharmacokinetics were calculated with the help of in silico methods. Results: Several such compounds showed better COX-2 binding than some commercial NSAIDs. PPDA+Z14 showed the best COX-2 binding affinity: (9:7 kcal=mol) with mild selectivity (2:4kcal=mol). The PPDA core displayed a general trend for enhanced COX-2 selectivity, and the introduction of halogen atoms or bulky aromatic substituents improved the affinity. All 25 prioritized compounds were both Lipinski Rule of 5 compliant and had good ADME profiles. Conclusions: In the present work, we have shown via computational approaches that promising amide-based lead compounds with a balanced COX-2 selectivity profile can be identified, which might provide anti-inflammatory effects with a low risk of cardiovascular events compared to very selective coxibs. The combination of the PPDA scaffold with selected substituents is therefore suggested as a privileged structure for the design of potentially less toxic anti-inflammatory agents, deserving of experimental investigation.
Keywords
Molecular docking; COX-1; COX-2; Selective inhibitors; Amide derivatives
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