title: Synthesis and biological evaluation of a new class of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.
abstract: A series of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential human 5-LOX and COX 1 and COX-2 inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 1) have been synthesized and the activity against COX-1, COX-2 and human 5-LOX enzymes has been evaluated. All the derivatives showed poor activity against enzymes. These data, together with our previous studies, indicated that phenidone and related compounds are not suitable as human 5-LOX inhibitors and that pyrazoline nucleus should not be considered a good scaffold for inhibitors of human 5-LOX enzyme, suggesting the necessity to revisit the proposed mechanism of action of phenidone (1) in human models.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Trieste, Piazzale Europa 1, I-34127, Trieste, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cusan
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Prato
authors.forename: Michael
authors.initials: M
authors.lastname: Adams
authors.forename: Antje
authors.initials: A
authors.lastname: Bodensieck
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Da Ros
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008565:Membrane Proteins; D015394:Molecular Structure; D009504:Neutrophils / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C503461:3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases