Abstract:
In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their
in vitro and in vivo anti-inflammatory potential. Amongst the synthesized compounds, compounds 7a, 7d
and 7f exhibited significant in vitro anti-inflammatory activity as compared to the standard etoricoxib.
Keeping this in mind, in vivo investigations were carried out via carrageenan induced inflammation and
acetic acid induced writhing models in male Wistar rats and compound 7a was found to possess appreciable anti-inflammatory and analgesic potential. The mode of action of compound 7a was also investigated
by using substance P as the biomarker, which shows promising results. Further, the selectivity of the most
active compound 7a against the cyclooxygenase enzyme was supported by molecular docking studies
which reveal that compound 7a has greater binding affinity towards COX-2 over COX-1 and 5-LOX enzymes. In silico ADME analysis of compound 7a confirms the drug-like characteristics and the in vivo acute
toxicity study showed the safety of the compound even up to a 2000 mg kg−1 dose. Thus, compound 7a
was identified as an effective anti-inflammatory agent, and can be explored for further analgesic/anti-inflammatory drug design and development.
