Abstract Background In the current study, various S -naproxen derivatives (NDs) were evaluated for their analgesic and anti-inflammatory activities using in vivo models, along with molecular docking studies. The analgesic potential was assessed through acetic acid-induced writhing, hot plate, and formalin-induced jumping tests. Anti-inflammatory effect was investigated using carrageenan-induced paw edema model. An acute toxicity study was also conducted to ensure safety. Results All tested NDs in different doses were found to be safe in the acute toxicity study. In the acetic acid-induced pain model, NDs (5 mg/kg) showed a significant ( p < 0.001) analgesic effect with compound 3 and 7 demonstrated maximum effect (80%). In hot plate test, compounds 7 , 8 , and 9 showed central analgesic activity with percent effects of 61, 48 and 45%, respectively ( p < 0.05). In formalin-induced pain model, all NDs demonstrated significant analgesic activity ( p < 0.001), with a stronger effect in the second phase of the test. For anti-inflammatory activity, NDs showed variable effects, with compound 7 (81.55%) and compound 8 (80.14%) showing the highest activity in the third hour of the carrageenan-induced paw edema model. Molecular docking studies confirmed strong interactions of NDs with both opioid receptors and COX-II enzymes, supporting their peripheral and central analgesic mechanisms. Conclusion The findings suggest that the tested S -naproxen derivatives exhibit significant analgesic and anti-inflammatory activities. The combination of in vivo and in silico data supports the analgesic and anti- inflammatory effects.
Muhammad et al. (Thu,) studied this question.