title: Design, synthesis and pharmacological evaluation of new anti-inflammatory compounds.
abstract: Inflammatory diseases and pain are among the main problems that significantly influence the lifestyle of millions of people and existing therapies are not always effective and can cause several adverse effects. In this context, the molecular modifications or synthesis of compounds continue being the best strategies for the identification of new compounds for the treatment of pain and inflammation. The aim of this study was to evaluate the analgesic and anti-inflammatory activities of new analogues of pyrazole compounds containing subunits N-phenyl-1-H-pirazoles and 1,3,4-oxadiazole-2(3H)-thione, LQFM-146, LQFM-147 and LQFM-148. In the acetic acid-induced abdominal writhing test, treatments with LQFM-146, LQFM-147 or LQFM-148 at doses 89, 178 and 356µmol/kg p.o. reduced the abdominal writhing in a dose-dependent manner. In the formalin test, these compounds at dose 178µmol/kg p.o. reduced the licking time only in inflammatory phase of this test, suggesting an antinociceptive effect dependent of the anti-inflammatory effect. The treatment with the three compounds in intermediate dose (178µmol/kg p.o.) reduced the edema at all tested time points in the carrageenan-induced paw edema test and reduced polymorphonuclears cell migration, activity myeloperoxidase and TNF-α levels in the carrageenan-induced pleurisy test. Our date suggest that the new compounds LQFM-146, LQFM-147 and LQFM-148 possess satisfactory anti-inflammatory and antinociceptive effects that involves the reduction of pro-inflammatory cytokines and inhibition of the myeloperoxidase enzyme.
authors: Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
authors: Amanda F
authors: AF
authors: Cidade
authors: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors: Patrícia A
authors: PA
authors: Vasconcelos
authors: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors: Daiany P B
authors: DPB
authors: Silva
authors: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.
authors: Iziara F
authors: IF
authors: Florentino
authors: Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil.
authors: Géssica A
authors: GA
authors: Vasconcelos
authors: Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry, Federal University of Goiás, Goiânia, GO, Brazil.
authors: Boniek G
authors: BG
authors: Vaz
authors: Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil. Electronic address: xico@ufg.br.
authors: Elson A
authors: EA
authors: Costa
authors: Chemistry Institute, Federal University of Goias, Campus Samambaia, Goiânia, GO, Brazil.
authors: Luciano M
authors: LM
authors: Lião
authors: Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil.
authors: Ricardo
authors: R
authors: Menegatti
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004487:Edema / Q000188:drug therapy; D008297:Male; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011720:Pyrazoles; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase
keywords: Inflammation; LQFM-146; LQFM-147, LQFM-148; Pyrazole compounds