Click chemistry synthesis, biological evaluation and docking study of some novel 2′-hydroxychalcone-triazole hybrids as potent anti-inflammatory agents.

• The efficient synthesis of the privileged intermediate 5-azido-2- hydroxyacetophenone. • The synthesis of 20 new 2′-hydroxychalcone-triazole hybrids some endowed with isatin. • Six compounds showed good in vivo anti-inflammatory activity with potent dual inhibition of COX-2 and 15-LOX. • Molecular docking studies disclosed important binding modes with COX-2 and 15-LOX. A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d , 6f , 6i , 8c , 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC 50 = 0.037–0.041 µM) and 15-LOX (IC 50 = 1.41–1.80 µM). Compounds 6i , 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d , 6f , 6i , 8c , 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15-LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]