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Design, synthesis and pharmacological assessment of new pyrazole compounds.
Oliveria, Jordana C; Silva, Daiany P B; Florentino, Iziara F; da Silva, Lidya C; Sanz, Germán; Vaz, Boniek G; Pazini, Francine; de Carvalho, Flávio S; Lião, Luciano M; Dos Santos, Thaís Rosa Marques; Valadares, Marize C; Costa, Elson A; Dos Santos, Fernanda Cristina Alcantara; Villavicencio, Bianca; Verli, Hugo; Menegatti, Ricardo.
Afiliación
  • Oliveria JC; Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiâniam, GO, Brazil.
  • Silva DPB; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
  • Florentino IF; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
  • da Silva LC; Laboratory of Chromatography and Mass Spectrometry (LaCEM), Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
  • Sanz G; Laboratory of Chromatography and Mass Spectrometry (LaCEM), Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
  • Vaz BG; Laboratory of Chromatography and Mass Spectrometry (LaCEM), Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
  • Pazini F; Institute of Health Sciences, Federal University of Mato Grosso, Sinop, MT, Brazil.
  • de Carvalho FS; Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiâniam, GO, Brazil.
  • Lião LM; Laboratory of Nuclear Magnetic Resonance, Chemistry Institute, Federal University of Goiás, Goiânia, GO, Brazil.
  • Dos Santos TRM; Laboratory of Pharmacology and Cell Toxicology, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
  • Valadares MC; Laboratory of Pharmacology and Cell Toxicology, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil.
  • Costa EA; Laboratory of Pharmacology of Natural and Synthetic Products, Department of Pharmacology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
  • Dos Santos FCA; Laboratory of Microscopy Applied to Reproduction, Department of Histology, Embryology and Cell Biology, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil.
  • Villavicencio B; Center of Biotechnology, Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil.
  • Verli H; Center of Biotechnology, Federal University of Rio Grande Do Sul, Porto Alegre, RS, Brazil.
  • Menegatti R; Laboratory of Medicinal Pharmaceutical Chemistry, College of Pharmacy, Federal University of Goiás, Goiâniam, GO, Brazil. rm_rj@yahoo.com.
Inflammopharmacology ; 28(4): 915-928, 2020 Aug.
Article en En | MEDLINE | ID: mdl-32529601
AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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 movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazoles Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Inflammopharmacology Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirazoles Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Inflammopharmacology Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2020 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza