Mohammad M. Al-Sanea, Abdelrahman Hamdi, Simone Brogi, Samar S. Tawfik, Dina I. A. Othman, Mahmoud Elshal, Hidayat Ur Rahman, Della G. T. Parambi, Rehab M. Elbargisy, Samy Selim, Ehab M. Mostafa, and Ahmed A. B. Mohamed
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.