In Silico, In Vitro, and In Vivo Antinociceptive Potential of S ‐Naproxen Derivatives

Selected naproxen derivatives were investigated for their antinociceptive effects, using in vitro (COX‐I/COX‐II antagonistic effect), in vivo (acetic acid and hot plate assay), and in silico (molecular simulation studies) approaches. The COX inhibition studies revealed that the maximum percent effect exhibited by GMO‐I‐111a 96.01 and 92% against COX‐2 and COX‐1, respectively, at higher concentrations. The effect at minimum concentration was 81 and 77% against COX‐1 and COX‐2, respectively. The COX antagonist effect of GMO‐I‐9a and GMO‐I‐11a was also outstanding in the acetic acid assay. All the tested derivatives demonstrated a significant ( p < 0.05) analgesic effect at all concentrations (1.25, 2.5, and 10 mg/kg). The maximum effect was found against GMO‐I‐135a (95%), followed by GMO‐I‐11a (92%). The central analgesic effect of various derivatives was significant ( p < 00.1). GMO‐I‐111a exhibited a significant ( p < 00.1) analgesic effect after 30 min at all the tested doses. The maximum effect at higher doses was shown by compound GMO‐I‐9a (93%) followed by GMO‐I‐11a (88%), GMO‐I‐111a (84%), and GMO‐I‐135a (78%). The latency time of GMO‐I‐9a and GMO‐I‐135a was significantly reversed by naloxone treatment, indicating the central analgesic effect. The molecular simulation studies showed that all the tested compounds had good binding interactions with COX‐1/COX‐2, except GMO‐I‐9a . In conclusion, the tested naproxen derivatives might have a significant analgesic effect.