Microwave synthesis of new naproxen analogues for chronic inflammation and their gastro-protective effect in post-operative model

In the present study, novel naproxen analogues (NS9-NS12) were synthesized under microwave irradiation and characterized by ¹H NMR, ¹³C NMR, and HR-ESI-MS advanced spectroscopic techniques. Their analgesic, anti-inflammatory and gastro-protective activities were evaluated in postoperative and chronic inflammatory pain models. Analgesic activity was determined by Eddy Hot plate and Acetic-induced Writhing tests using dose of 30 mg/kg (b.wt), while anti-inflammatory activity was determined by Egg induced method. Additionally, dose 1, 3, 10 and 30 mg/kg (b.wt) were used for post-operative pain and ulcerogenicity was assessed at 100 and 150 mg/kg(b.wt) after finding that all naproxen analogues were safe. Among all analogues, NS12 showed high significant (p < 0.001 increase in paw latency, inhibition in of writhing and significant (p < 0.001) edema reduction in subplantar area after 4 h of egg-induced edema. NS12 also significantly (p < 0.001) reduced postoperative pain and inflammation in both acute and repeated testing studies when compared to other analogues and untreated group. Histological and biochemical characteristics confirmed that naproxen derivatives exhibited minimal ulcerogenicity at 100 and 150 mg/kg (b.wt) in comparison to aspirin and naproxen. Based on these findings, synthesized naproxen analogues, particularly NS12 demonstrated potent analgesic and anti-inflammatory properties with enhanced gastric safety, indicating their potential as safer therapeutic alternatives to traditional naproxen for the treatment of pathological disorders associated with inflammation and pain.