Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition.

In the present work, coumarin based pyrazolines () have been synthesized and investigated for their and anti-inflammatory potential. Amongst the synthesized compounds, compounds , and exhibited significant anti-inflammatory activity as compared to the standard etoricoxib. Keeping this in mind, investigations were carried out carrageenan induced inflammation and acetic acid induced writhing models in male Wistar rats and compound was found to possess appreciable anti-inflammatory and analgesic potential. The mode of action of compound was also investigated by using substance P as the biomarker, which shows promising results. Further, the selectivity of the most active compound against the cyclooxygenase enzyme was supported by molecular docking studies which reveal that compound has greater binding affinity towards COX-2 over COX-1 and 5-LOX enzymes. ADME analysis of compound confirms the drug-like characteristics and the acute toxicity study showed the safety of the compound even up to a 2000 mg kg dose. Thus, compound was identified as an effective anti-inflammatory agent, and can be explored for further analgesic/anti-inflammatory drug design and development.