Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives
This work deals with an efficient and straightforward synthesis, biological activity and molecular docking study of novel 1,4-benzoxazine derivatives. Dehydrocyclization through consecutive functionalization of –OH and –NH bond of 2-aminophenol derivative with disubstituted alkyne in presence of [RuCl2(p-cymene)]2 as catalyst allows synthesis of 1,4-benzoxazine derivative in single synthetic step. All the synthesized compounds (3a–3s) were evaluated for their in vitro cyclooxygenase isoenzymes (COX-1/COX-2) inhibition assay. The results of the assay indicated that compounds 3e, 3f, 3r, and 3s exhibited optimal COX-2 inhibition, with IC50 values of 0.57–0.72 μM, and selectivity index (SI) range of 186.8–242.4, using Celecoxib as a standard drug (IC50 = 0.30 μM; COX-2 SI: >303). Further, the molecular docking study explored the essential binding mode and possible interactions within the binding site of COX-1/COX-2 isoenzymes. This study identified the potential compounds, which can be promising leads for their subsequent development as newer anti-inflammatory agents.