Novel Pyrazole-3-Cyano-2-Pyridinone Hybrids as Multitarget Anti-Inflammatory Agents: Synthesis, Computational Modeling, and Biological Evaluation

Introduction: The development of multi-target anti-inflammatory agents represents a promising strategy to improve therapeutic efficacy while minimizing adverse effects associated with single-target drugs. In this study, a rational hybridization approach was employed to design pyrazole/3-cyano-2-pyridinone hybrids aimed at modulating key inflammatory mediators. Methods: , and TNF-α inhibition assays were performed. Cytotoxicity was determined using MTT assays. Molecular docking and 100-ns molecular dynamics (MD) simulations were conducted to investigate binding modes and stability, while in silico ADME profiling was used to predict pharmacokinetic properties. Results: with COX-2, 5-LOX, and iNOS, respectively. In silico pharmacokinetic analysis predicted good oral bioavailability and drug-like properties. Conclusion: The synthesized pyrazole/3-cyano-2-pyridinone hybrids demonstrated promising multi-target anti-inflammatory activity with favorable safety and pharmacokinetic profiles, highlighting their potential as lead candidates for further development.