Rational Design of Biodegradable Sulphonamide Candidates Treating Septicaemia by Synergistic Dual Inhibition of COX-2/PGE2 Axis and DHPS Enzyme

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Jun 16

PMID 35707920

Authors

Nada H El-Dershaby

Soad A El-Hawash

Shaymaa E Kassab

Hoda G Dabees

Ahmed E Abdel Moneim

Ibrahim A Abdel Wahab

Mohammad M Abd-Alhaseeb

Mostafa M M El-Miligy

Affiliations

Soon will be listed here.

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 and demonstrated potent COX-2 inhibitory activity comparable to celecoxib. and exhibited ED lower than celecoxib in carrageenan-induced paw edoema test with % PGE2 inhibition higher than celecoxib. Furthermore, , and showed gastric safety profile like celecoxib. Moreover, antibacterial screening revealed that, showed activity against higher than sulfasalazine. While, revealed activity against higher than sulfasalazine and against comparable to sulfasalazine. Compound achieved the target goal as potent inhibitor of COX-2/PGE2 axis and broad-spectrum antibacterial activity against induced septicaemia in mice.

Citing Articles

Rational Design and Synthesis of New Selective COX-2 Inhibitors with In Vivo PGE2-Lowering Activity by Tethering Benzenesulfonamide and 1,2,3-Triazole Pharmacophores to Some NSAIDs.

El-Dershaby N, El-Hawash S, Kassab S, Daabees H, Abdel Moneim A, El-Miligy M Pharmaceuticals (Basel). 2022; 15(10).

PMID: 36297278 PMC: 9609428. DOI: 10.3390/ph15101165.

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