Synthesis, anti-inflammatory, cytotoxic, and COX-1/2 inhibitory activities of cyclic imides bearing 3-benzenesulfonamide, oxime, and β-phenylalanine scaffolds: a molecular docking study.

Cyclic imides containing 3-benzenesulfonamide, oxime, and β-phenylalanine derivatives were synthesised and evaluated to elucidate their anti-inflammatory and ulcerogenic activity and cytotoxic effects. Most active anti-inflammatory agents were subjected to COX-1/2 inhibition assay. 3-Benzenesulfonamides (, and ), oximes (), and β-phenylalanine derivative () showed potential anti-inflammatory activities with 71.2-82.9% oedema inhibition relative to celecoxib and diclofenac (85.6 and 83.4%, respectively). Most active cyclic imides , , , , and possessed ED of 35.4-45.3 mg kg relative to that of celecoxib (34.1 mg kg). For the cytotoxic evaluation, the selected derivatives and exhibited weak positive cytotoxic effects (PCE = 2/59-5/59) at 10 μM compared to the standard drug, imatinib (PCE = 20/59). Cyclic imides bearing 3-benzenesulfonamide (, and ), acetophenone oxime (, , and ) exhibited high selectivity against COX-2 with SI > 55.6-333.3 relative to that for celecoxib [SI > 387.6]. β-Phenylalanine derivatives and were non-selective towards COX-1/2 isozymes as indicated by their SI of 0.46-0.68.