Add time:07/23/2019         Source:sciencedirect.com

We have reported riparin (cas 112356-54-4) 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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