title: Cyclooxygenase-2 and 15-lipoxygenase inhibition, synthesis, anti-inflammatory activity and ulcer liability of new celecoxib analogues: Determination of region-specific pyrazole ring formation by NOESY.
abstract: Two new series of 1,5-diaryl pyrazoline (3a-f) and 1,5-diaryl pyrazole (5a and 5b) were designed as both COX-2 and 15-LOX inhibitors. All the prepared compounds were fully characterized by all spectral and element analysis. Their anti-inflammatory activity and ulcer index were included. Pyrazoline 3f is the most effective with IC50=1.14 and 4.7μM against COX-2 and 15-LOX respectively, and more potent than celecoxib and meclofenamate references. In addition 3a, 3b, 5a, and 5b were safer with low ulcer index than celecoxib. Docking study was performed for the most active compounds such as 2b, 3a, and 3f on COX-2 and 15-LOX enzymes.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: eman.ahmed@pharm.bsu.edu.eg.
authors.forename: Eman K A
authors.initials: EKA
authors.lastname: Abdelall
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
authors.forename: Phoebe F
authors.initials: PF
authors.lastname: Lamie
authors.affiliation: Department of Biochemistry, Cairo General Hospital, Cairo, Egypt.
authors.forename: Waleed A M
authors.initials: WAM
authors.lastname: Ali
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D000068579:Celecoxib / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D001093:Arachidonate 15-Lipoxygenase; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: 15-Lipoxygenase inhibitors; Antiinflammatory; Cyclooxygenase inhibitors; Diethyl oxalate; Sulfonamide pharmacophores