Computational Design of Dual COX-2/ LOX Inhibitors as Safer Anti-Inflammatory Agents

Inflammatory disorders remain a major global health challenge, with current nonsteroidal anti-inflammatory drugs (NSAIDs) often limited by gastrointestinal and cardiovascular side effects. Selective cyclooxygenase-2 (COX-2) inhibitors reduce inflammation but can disrupt prostaglandin balance, while lipoxygenase (LOX) inhibitors alone fail to fully address the complex arachidonic acid cascade. To overcome these limitations, dual COX-2/LOX inhibitors have emerged as promising therapeutic agents capable of modulating multiple inflammatory pathways simultaneously. In this study, we employ computational design strategies—including molecular docking, pharmacophore modeling, and ADMET profiling—to identify novel scaffolds with dual inhibitory potential. Structural insights reveal key binding interactions within COX-2 and 5-LOX active sites, guiding rational optimization of lead compounds. In silico toxicity and drug-likeness assessments further support the safety profile of these candidates compared to conventional NSAIDs. Our findings highlight the feasibility of computational approaches in accelerating the discovery of safer, more effective anti-inflammatory agents, paving the way for future experimental validation and clinical translation.