Design, Synthesis, In Silico Docking, Multitarget Bioevaluation and Molecular Dynamic Simulation of Novel Pyrazolo3,4-dPyrimidinone Derivatives as Potential In Vitro and In Vivo Anti-Inflammatory Agents
In vitro experiments showed significant anti-inflammatory effects through COX-2 inhibition, suggesting these compounds may be viable therapeutic options.
Key Points
Compound 5k demonstrated substantial anti-inflammatory efficacy by inhibiting COX-2 and reducing TNF-α and IL-6 levels.
The most potent compound, 5k, had an IC50 of 2.34 μM and a selectivity index of 95.8 compared to COX-1.
Molecular dynamic simulation confirmed that compound 5k showed enhanced binding free energy of -10.57 kcal/mol with COX-2.
In vivo testing indicated compound 5j and 5k effectively reduced paw edema compared to indomethacin, showcasing excellent safety profiles.