Portal de Periódicos da CAPES

Artigo Produção Nacional Revisado por pares

BIBTEX RIS

Structural and spectroscopic analysis, ADMET study, and anxiolytic-like effect in adult zebrafish (Danio rerio) of 4′-[(1E,2E)-1-(2-(2′,4′-dinitrophenyl)hydrazone-3-(4-methoxyphenyl)allyl)aniline

2021; Elsevier BV; Volume: 1251; Linguagem: Inglês

10.1016/j.molstruc.2021.132064

1872-8014

Mikael Amaro de Souza, Kevin K.A. de Castro, Francisco Wagner Queiroz Almeida-Neto, Paulo Nogueira Bandeira, Maria Kueirislene Amâncio Ferreira, Márcia Machado Marinho, Matheus Nunes da Rocha, Débora Hellen Almeida de Brito, Francisco Rogênio da Silva Mendes, Tigressa Helena Soares Rodrigues, Mateus Rodrigues de Oliveira, Jane Eire Silva Alencar de Menezes, Antônio C.H. Barreto, Emmanuel Silva Marinho, Pedro de Lima‐Neto, Hélcio Silva dos Santos, Alexandre Magno Rodrigues Teixeira,

Photochromic and Fluorescence Chemistry

Benzodiazepines (GABA receptor agonists) and serotonin reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of anxiety. However, they have considerable adverse effects, so it is important to discover new anxiolytic agents. In this work, the 4′-[(1E,2E)-1-(2-(2′,4′-dinitrophenyl)hydrazone-3-(4-methoxyphenyl)allyl)aniline (HYDRAZDN) was synthesized and characterized by 1H and 13C NMR, 2D-NMR, ATR-FTIR, FT-Raman, and UV–Vis spectroscopy, and their structural and spectroscopic proprieties were evaluated by quantum chemistry theoretical calculations. Properties such as drug-likeness and pharmacokinetics were also estimated. The anxiolytic-like effect of the compound was also evaluated using adult zebrafish (Danio rerio). The results showed that the HYDRAZDN compound caused a reduction in zebrafish locomotor activity and induced maximum permanence of zebrafish in the clear zone at a dose of 40 mg/kg, an effect similar to the effect of positive control diazepam (DZP: 40 mg/kg). To identify the mechanism of action of the anxiolytic effect of this compound, we used flumazenil, an antagonist at the benzodiazepine binding site at GABAA receptors. The treatment with the highest dose of HYDRAZDN (40 mg/kg) and DZP (40 mg/kg) caused anxiolytic behavior in the animals that spent most of their time in the dark region of the aquarium. This effect was reduced by flumazenil, indicating that anxiolytic activity of the synthesized hydrazone occurs through the GABAergic system.