Novel benzenesulfonamide and 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives as potential selective COX-2 inhibitors
RIS ID
134468
Abstract
Two new series of 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives containing either five membered heterocyclic rings or aryl hydrazones were synthesized and evaluated for their in vitro COX-1/COX-2 inhibitory activity. In vivo anti-inflammatory evaluation revealed that benzenesulfonamides bearing pyrazole moiety 19, 20 and its cyclized form 23 exhibited the highest anti-inflammatory activity with comparable potency to celecoxib. Furthermore, the ulcerogenic activity evaluation showed that compounds 19, 20 and 23 exerted the minimal ulcer index in comparison to indomethacin as a reference drug. Docking studies of the most selective COX-2 derivatives were also carried out against COX-2 active site. Benzenesulfonamide derivatives 19 and 20 displayed higher predicted binding affinities inside the COX-2 active site. Molecular modelling simulation and drug likeness studies showed good agreement with the obtained biological evaluation.
Publication Details
Taher, E. S., Ibrahim, T. S., Fares, M., AL-Mahmoudy, A. M. M., Radwan, A. F., Orabi, K. Y. & El-Sabbagh, O. I. (2019). Novel benzenesulfonamide and 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives as potential selective COX-2 inhibitors. European Journal of Medicinal Chemistry, 171 372-382.