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

Abstract

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.

Keywords: Naproxen Derivatives, Molecular, Analgesic Effect, Silico, Vitro