In the current studies two
naproxen derivatives (
NPD) were evaluated for
analgesic and anti-inflammatory properties. The
acetic acid and hot plate animal models were used to screen the compounds for
analgesic potential. While the anti-inflammatory potential was evaluated through animal paw
edema, induced by several inflammatory mediators (
carrageenan,
bradykinin, and
prostaglandin E2), the
xylene-induced ear
edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the
acetic acid-induced writhing paradigm. In the case of the hot plate, the
NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of
NPD 1 was 87.53. The
naloxone injection significantly lowered the latency time of
NPD 1 as compared to
NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw
edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of
NPD 1 was better. The maximal percent inhibition by
NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from
xylene-induced ere
edema. Further, a molecular docking study was carried out to investigate the binding modes of the
NPD. The docking analysis revealed that the
NPD significantly interacted with the COX2
enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two
naproxen derivatives.