Abstract
This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall-Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell...Continue Reading
References
Sep 1, 1989·Pain·Manabu ShibataReizo Inoki
Jul 1, 1987·The Journal of Pharmacy and Pharmacology·A VillarM J Alcaraz
Jul 1, 1987·Pain·S Hunskaar, K Hole
Mar 28, 1997·Journal of Medicinal Chemistry·M E ZwaagstraM Q Zhang
Jun 27, 1998·Toxicon : Official Journal of the International Society on Toxinology·K A ShiomiY Nagashima
Dec 1, 1962·Proceedings of the Society for Experimental Biology and Medicine·C A WINTERG W NUSS
Apr 6, 2007·International Journal of Experimental Pathology·Toby Lawrence, Derek W Gilroy
Dec 25, 2007·Pharmacology & Therapeutics·Daniel TraceyPaul P Tak
Mar 23, 2010·Cell·Ruslan Medzhitov
May 12, 2010·Cold Spring Harbor Perspectives in Biology·Toby Lawrence
Sep 30, 2010·Proteins·Juliana I dos SantosMarcos R M Fontes
Apr 8, 2011·The FEBS Journal·Tse Siang KangR Manjunatha Kini
Jul 13, 2011·Journal of Biochemistry·Makoto MurakamiKei Yamamoto
Aug 15, 2012·Journal of Cheminformatics·Marcus D HanwellGeoffrey R Hutchison
Dec 12, 2012·The Journal of Pharmacy and Pharmacology·Roberta Campos LinoElson Alves Costa
Mar 3, 2015·European Respiratory Review : an Official Journal of the European Respiratory Society·Cindy Barnig, Bruce D Levy
Apr 16, 2015·Nucleic Acids Research·Sebastian SalentinMichael Schroeder
Jul 21, 2015·PloS One·Carlos A H FernandesMarcos R M Fontes
Feb 8, 2011·Journal of Chemical Theory and Computation·Mats H M OlssonJan H Jensen
Aug 17, 2016·Chemical Biology & Drug Design·Lanussy Porfiro de OliveiraElson Alves Costa
Oct 30, 2016·European Journal of Pharmacology·Amanda F CidadeRicardo Menegatti
Apr 17, 2017·Nitric Oxide : Biology and Chemistry·Iziara F FlorentinoElson A Costa
Nov 22, 2017·Signal Transduction and Targeted Therapy·Ting LiuShao-Cong Sun
Jan 18, 2018·Archives of Biochemistry and Biophysics·Yasuaki Aratani
Apr 20, 2018·Medical Sciences : Open Access Journal·Amjad A KhanArshad H Rahmani
May 23, 2018·Nucleic Acids Research·Andrew WaterhouseTorsten Schwede
Mar 7, 2019·Advances in Pharmacological Sciences·Rebecca S Y Wong
May 6, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Iziara F FlorentinoJan Tytgat