Title

Novel benzenesulfonamide and 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives as potential selective COX-2 inhibitors

RIS ID

134468

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.

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.

Please refer to publisher version or contact your library.

Share

COinS
 

Link to publisher version (DOI)

http://dx.doi.org/10.1016/j.ejmech.2019.03.042