Synthesis of Paracetamol-Appended Bis 1,2,3-Triazole Analogues as Anti-Inflammatory Agents

Paracetamol-based bis 1,2,3-triazole analogues were synthesized involving copper-catalyzed click chemistry protocol. The new compounds were characterized by 1H NMR, 13C NMR, and mass spectral techniques. All the compounds were evaluated for their in vitro anti-inflammatory properties using diclofenac as standard reference. The compound 6b with chlorine and fluorine functions displayed outstanding activity with IC50 values of 7.34 +/- 0.45 mu M and 7.84 +/- 0.47 mu M, respectively. Compound 6g with methyl and fluorine functions displayed best activity with IC50 values of 9.34 +/- 0.22 mu M and 9.40 +/- 0.35 mu M, respectively. Compound 6i, 6k, 6f, 6a, 6e, 6h, 6j, and 6l exhibited promising activity with respect to diclofenac. Using PyRx tool, the molecular docking study against crystal structure of COX-2 proved the binding efficacies with notable binding interactions.