| Autor: |
El-Dershaby NH; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt., El-Hawash SA; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Kassab SE; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.; Department of organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufia,Egypt., Dabees HG; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt., Abdel Moneim AE; Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt., Abdel Wahab IA; Microbiology and Immunology Department, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt., Abd-Alhaseeb MM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhur University, Damanhour, Egypt., El-Miligy MMM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. |
| Abstrakt: |
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. |
