| Autor: |
Said MF; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, PO Box 11562, Egypt., Moussa BA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, PO Box 11562, Egypt., Mahrouse MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, PO Box 11562, Egypt., Marie SM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, PO Box 11562, Egypt., Mohamed NM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Modern University for Technology & Information MTI, Cairo, Egypt. |
| Abstrakt: |
Background: Dual COX/5-LOX inhibition is a bright strategy for developing new potent and safe anti-inflammatory agents. Methods: New imines were synthesized and evaluated for their anti-inflammatory activity. The most active compounds were further investigated for their safety profile. Their molecular docking and physicochemical parameters were assessed. A new LC-MS/MS method was developed for the quantification of compound 4d in rat plasma. Results: Synthesized compounds were found to have anti-inflammatory activity (77-88% edema inhibition). In addition, 4d , 5m and 7d showed analgesic activity (92.50, 95.71 and 96.28% protection, respectively). 4d showed dual COX-2/5-LOX activity. Molecular docking expected the binding pattern of compounds in COX-1, COX-2 and 5-LOX active sites. The in vivo pharmacokinetic parameters of compound 4d were also obtained. |
