Rational design of biodegradable sulphonamide candidates treating septicaemia by synergistic dual inhibition of COX-2/PGE2 axis and DHPS enzyme.

ABSTRACT: A new series of co-drugs was designed based on hybridising the dihydropteroate synthase (DHPS) inhibitor sulphonamide scaffold with the COX-2 inhibitor salicylamide pharmacophore through biodegradable linkage to achieve compounds with synergistic dual inhibition of COX-2/PGE2 axis and DHPS enzyme to enhance antibacterial activity for treatment of septicaemia. Compounds 5 b, 5j, 5n and 5o demonstrated potent in vitro COX-2 inhibitory activity comparable to celecoxib. 5j and 5o exhibited ED₅₀ lower than celecoxib in carrageenan-induced paw edoema test with % PGE2 inhibition higher than celecoxib. Furthermore, 5 b, 5j and 5n showed gastric safety profile like celecoxib. Moreover, in vivo antibacterial screening revealed

SUBMITTER: El-Dershaby NH 

PROVIDER: S-EPMC9225712 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature