title: Synthesis of 1,5-diarylpyrazol-3-propanoic acids towards inhibition of cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4 formation.
abstract: A set of 25 derivatives of 3-[1-(6-substituted-pyridazin-3-yl)-5-(4-substituted-phenyl)-1H-pyrazol-3-yl]propanoic acids has been synthesized and evaluated for their in vitro cyclooxygenase-1/2 (COX-1/ 2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes as well as for their 5-lipoxygenase (5-LO)-mediated LTB4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes (PMNL). Among the synthesized compounds, especially 4g showed COX-1 (IC50 = 1.5 microM) and COX-2 (IC50 = 1.6 microM) inhibitory activity, whereas compounds 4 b and 4 f resulted in the inhibition of 5-LO-mediated LTB4 formation at 14 microM and 12 microM IC50 values, respectively, without any significant inhibition on COX isoforms.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey.
authors.forename: Burcu Calişkan Ergün
authors.initials: BC
authors.lastname: Ergün
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Nuñez
authors.forename: Luis
authors.initials: L
authors.lastname: Labeaga
authors.forename: Francisco
authors.initials: F
authors.lastname: Ledo
authors.forename: Janice
authors.initials: J
authors.lastname: Darlington
authors.forename: Gretchen
authors.initials: G
authors.lastname: Bain
authors.forename: Bilge
authors.initials: B
authors.lastname: Cakir
authors.forename: Erden
authors.initials: E
authors.lastname: Banoglu
mesh_terms: D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D011422:Propionates / Q000138:chemical synthesis* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007202:Indicators and Reagents; D016859:Lipoxygenase Inhibitors; D011422:Propionates; D011720:Pyrazoles; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2