Design, synthesis, and biological investigation of oxadiazolyl, thiadiazolyl, and pyrimidinyl linked antipyrine derivatives as potential non-acidic anti-inflammatory agents. (31st December 2023)

• Record Type: Journal Article
• Authors: Al-Sanea, Mohammad M.; Hamdi, Abdelrahman; Brogi, Simone; S. Tawfik, Samar; Othman, Dina I. A.; Elshal, Mahmoud; Ur Rahman, Hidayat; Parambi, Della G. T.; M. Elbargisy, Rehab; Selim, Samy; Mostafa, Ehab M.; Mohamed, Ahmed A. B.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 38:Number 1(2023)
• Publication Date: 2023-12-31
• Subjects: Antipyrine -- oxadiazole -- thiadiazole -- pyrimidine -- anti-inflammatory; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2162511
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A novel series of 12 antipyrine derivatives containing 1, 3, 4-oxadiazoles (4a-d), 1, 3, 4-thiadiazoles (6a -d), and pyrimidines (8a -d), was preparedand assessed for its potential in vitro COX-2 inhibitors. Compared to Celecoxib, compounds 4b-d and 8d were the most potent derivatives c with a half-maximal inhibitory concentration range of 53–69 nM. Considering COX-2 selectivity index, compounds 4 b and 4c were chosen among these most potent derivatives for further investigation. The in vivo ability of compounds 4 b and 4c to counteract carrageenan-induced paw edoema has been assessed and their potential underlying mechanisms have been elucidated and the results have been further validated using molecular docking simulations.