title: Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: design, synthesis and evaluation as potential anti-inflammatory agents.
abstract: Novel series of celecoxib analogs endowed with benzofuran moiety 3a-e and 9a-d were synthesized and evaluated for COX-1/COX-2 inhibitory activity in vitro. The most potent and selective COX-2 inhibitors - compounds 3c, 3d, 3e, 9c and 9d - were assessed for their anti-inflammatory activity and ulcerogenic liability in vivo. The 3-(pyridin-3-yl)pyrazole derivatives 3c and 3e exhibited the highest anti-inflammatory activity, that is equipotent to celecoxib. Furthermore, the tested compounds proved to have better gastric safety profile compared to celecoxib. In particular, compound 3e demonstrated about 40% reduction in ulcerogenic potential relative to the reference drug. Finally, molecular docking simulation of the new compounds in COX-2 active site and drug likeness studies showed good agreement with the obtained pharmaco-biological results.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
authors.forename: Ghaneya Sayed
authors.initials: GS
authors.lastname: Hassan
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt. Electronic address: saharshaarawy_69@yahoo.com.
authors.forename: Sahar Mahmoud
authors.initials: SM
authors.lastname: Abou-Seri
authors.affiliation: Pharmacology Department, Faculty of Veterinary, Cairo University, Egypt.
authors.forename: Gehan
authors.initials: G
authors.lastname: Kamel
authors.affiliation: Biochemistry Department, Division of Genetic Engineering and Biotechnology, National Research Centre, Cairo, Egypt.
authors.forename: Mamdouh Moawad
authors.initials: MM
authors.lastname: Ali
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
keywords: Anti-inflammatory agents; Benzofuran; COX-1/COX-2 inhibitory activity; Celecoxib analogs; Pyrazole