Produção Nacional
Revisado por pares
Pathophysiological investigations, anxiolytic effects and interaction of a semisynthetic riparin with benzodiazepine receptors
2018; Elsevier BV; Volume: 103; Linguagem: Inglês
10.1016/j.biopha.2018.04.130
ISSN1950-6007
AutoresÉverton José Ferreira de Araújo, Luís Mário Rezende Júnior, Layana Karine Farias Lima, Marcelo Pereira da Silva-Júnior, Oskar Almeida Silva, Benedito Pereira de Sousa Neto, Antônia Amanda Cardoso de Almeida, Stanley Juan Chavéz Gutierrez, Adriana da Rocha Tomé, Luciano da Silva Lopes, Paulo Michel Pinheiro Ferreira, Francisco das Chagas Alves Lima,
Tópico(s)Insect and Pesticide Research
ResumoWe have reported Riparin A as a promising antiparasitic molecule against Leishmania amazonensis promastigotes. This work evaluated the acute oral toxicity of Riparin A and its anxiolytic effects using in vivo models and computational tools. Mice were submitted to acute oral toxicity tests (Guideline OECD 423). Later, anxiety assays with Riparin A (50, 100 and 200 mg/kg: elevated plus maze, light/dark box and marble burying) were performed. Theoretical calculations analyzed interaction of Riparin A with gamma-amino butyric acid (GABA) receptors. Only Riparin A at 2000 mg/kg alter body weight, food and water consumption and urine production after 7 and/or 14 days treatment and increased serum triglycerides. There was increase in the time spent in the open arms (TSOA) and number of transitions between compartments (NTC) and decrease in number of hidden balls (NHB) in Riparin A-treated animals at 200 mg/kg (P < 0.05), whose approximate ED50 was 283.1 (156.5–397.1) mg/kg. The functional amide of Riparin A interacted with the GABAA receptor mainly at subunits α2 and β1 and presented strong interaction with the Asp68 residue, which is part of the pharmacophore group. Riparin A was toxically safe and pharmacologically active for anxiolytic purposes, revealed NOAEL of 200 mg/kg and probably interacts with Asp68 residues of benzodiazepine receptors by hydrogen bonds.
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