GABA A receptor participation in anxiolytic and anticonvulsant effects of (E)-3-(furan-2-yl)-1-(2hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one in adult zebrafish.

Autor: Silva Mendes FR; Department of Biological Chemistry, Regional University of Cariri, CE, Brazil., Wlisses da Silva A; State University of Ceara, Graduate Program of Biotechnology, Fortaleza, CE, Brazil., Amâncio Ferreira MK; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., de Lima Rebouças E; Department of Biological Chemistry, Regional University of Cariri, CE, Brazil., Marinho EM; Federal University of Ceara, Department of Analytical and Physical Chemistry, Fortaleza, CE, Brazil., Marinho MM; State University of Ceara, Iguatu Faculty of Education, Science and Letters, Iguatu, CE, Brazil., Bandeira PN; State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil., Rodrigues Teixeira AM; Department of Biological Chemistry, Regional University of Cariri, CE, Brazil., Silva Alencar de Menezes JE; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil., Alves de Siqueira E; Federal University of Ceará, Department of Clinical and Toxicological Analysis, Fortaleza, CE, Brazil., Róseo Paula Pessoa Bezerra de Menezes R; Federal University of Ceará, Department of Clinical and Toxicological Analysis, Fortaleza, CE, Brazil., Marinho ES; State University of Ceara, Department of Chemistry, Limoeiro do Norte, CE, Brazil., Silva Dos Santos H; Department of Biological Chemistry, Regional University of Cariri, CE, Brazil; State University of Ceara, Graduate Program of Biotechnology, Fortaleza, CE, Brazil; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil; State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil. Electronic address: helcio_santos@uvanet.br.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2022 May; Vol. 155, pp. 105303. Date of Electronic Publication: 2022 Feb 17.
DOI: 10.1016/j.neuint.2022.105303
Abstrakt: Anxiety is a mental disorder that affects 25% of patients with epilepsy, and treatments for anxiety and seizures involve the use of benzodiazepines, a class of drugs that have many adverse effects such as decreased motor coordination, drowsiness, and sedation. Thus, new types of drugs with minimal side effects are of immediate requirement. Chalcones comprise a class of compounds with important therapeutic potential and have recently been investigated for their potential as anxiolytic and anticonvulsant agents. Therefore, this study aimed to evaluate the anxiolytic and anticonvulsant effects of the synthetic chalcone (E)-3-(furan-2-yl)-1-(2hydroxy-3,4,6-trimethoxyphenyl)prop-2-en-1-one (FURCHAL) using adult zebrafish as an animal model. Anxiolytic potential was assessed using the light/dark test and the anticonvulsant effect in 3-stage pentylenetetrazol (PTZ)-induced seizure tests. The mechanisms of the anxiolytic effect were analyzed using γ-aminobutyric acid (GABA) and the serotoninergic system. The anxiolytic effect of FURCHAL was verified by a reduction in fish locomotion, similar to diazepam (DZP), which may involve the GABA A receptor, as there was no reversal in the anxiolytic behavior of animals treated with FURCHAL by serotonergic antagonists. In addition, pretreatment with flumazenil blocked the anticonvulsant effect of FURCHAL and DZP at all three stages, indicating that FURCHAL also has anticonvulsant effects and that the presence of the α,β unsaturated aromatic system and heterocyclic moiety in FURCHAL provided greater affinity for the GABA A receptors. Molecular docking revealed that the interactions involved in the formation of the protein-binding complex FURCHAL-GABA A are formed by three H-bonds involving the oxygen atoms of FURCHAL, and notably, complexes operated in the same region of the DZP site. Thus, this study adds new evidence and highlights that FURCHAL can potentially be used to develop compounds with anxiolytic and anticonvulsant properties.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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