C-2 derivatized 8-sulfonamidoquinolines as antibacterial compounds

Davison, Emma K.; McGowan, John E.; Li, Freda F.; Harper, Andrew D.; Jeong, Joo Young; Mros, Sonya; Harbison-Price, Nichaela; Zuylen, Essie M. Van; Knottenbelt, Melanie K.; Heikal, Adam; Ferguson, Scott; McConnell, Michelle; Cook, Gregory M.; Krittaphol, Woravimol; Walker, Greg F.; Brimble, Margaret A.; Rennison, David

doi:10.1016/j.bmc.2020.115837

Cited by 2 publications

(1 citation statement)

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“…Additionally, the sulphonamide moiety constitutes the prime pharmacophore of most selective COX-2 inhibitors as celecoxib and its derivatives 16 . In fact, sulphonamides comprise an interesting class of drugs with a wide scope of pharmacological activities such as antibacterial 17 , 18 , hypoglycemic 19 , diuretic 20 , carbonic anhydrase enzyme inhibitory properties 21–24 , antithyroid 25 and anti-inflammatory agents 26 . This may be attributed to sulphonamides' phenylamino and sulphonyl amino groups essential for various biological activities as well as metal coordination 27 .…”

Section: Introductionmentioning

confidence: 99%

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

El-Dershaby

El-Hawash

Kassab

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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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 ED 50 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 that, 5j showed activity against S.aureus and E.coli higher than sulfasalazine. While, 5o revealed activity against E.coli higher than sulfasalazine and against S.aureus comparable to sulfasalazine. Compound 5j achieved the target goal as potent inhibitor of COX-2/PGE2 axis and in vivo broad-spectrum antibacterial activity against induced septicaemia in mice.

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