| Autor: |
Cesário HPSF; Department of Organic and Inorganic Chemistry, Science Center, Federal University of Ceará, Fortaleza, CE, Brazil., Silva FCO; Laboratory of Chemistry of Natural Products, Ceará State University, Fortaleza, CE, Brazil., Ferreira MKA; Laboratory of Chemistry of Natural Products, Ceará State University, Fortaleza, CE, Brazil., de Menezes JESA; Laboratory of Chemistry of Natural Products, Ceará State University, Fortaleza, CE, Brazil., Dos Santos HS; Laboratory of Chemistry of Natural Products, Synthesis and Biocatalysis of Organic Compounds, Vale do Acaraú University, Sobral, CE, Brazil., Marques da Fonseca A; Academic Master in Sociobiodiversity and Sustainable Technologies - MASTS, Institute of Engineering and Sustainable Development, University of International Integration of Afro-Brazilian Lusofonia, Acarape, CE, Brazil., Nogueira CES; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Department of Physics, Regional University of Cariri, Crato, CE, Brazil., Marinho MM; Laboratory of Chemistry of Natural Products, Synthesis and Biocatalysis of Organic Compounds, Vale do Acaraú University, Sobral, CE, Brazil., Marinho ES; Course of Physics, State University of Ceará, Fortaleza, CE, Brazil., Teixeira AMR; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Course of Physics, State University of Ceará, Fortaleza, CE, Brazil., Silveira ER; Department of Organic and Inorganic Chemistry, Science Center, Federal University of Ceará, Fortaleza, CE, Brazil., Pessoa ODL; Department of Organic and Inorganic Chemistry, Science Center, Federal University of Ceará, Fortaleza, CE, Brazil. |
| Abstrakt: |
General anxiety disorders are among the most prevalent mental health problems worldwide. The emergence and development of anxiety disorders can be due to genetic (30-50%) or non-genetic (50-70%) factors. Despite medical progress, available pharmacotherapies are sometimes ineffective or can cause undesirable side effects. Thus, it becomes necessary to discover new safe and effective drugs against anxiety. This study evaluated the anxiolytic effect in adult zebrafish ( Danio rerio ) of a natural pyrroloformamide (PFD), N -(4,5-dihydro-5-oxo-1,2-dithiolo-[4,3,b]-pyrrole-6-yl)- N -methylformamide, isolated from a Streptomyces sp. bacterium strain recovered from the ascidian Eudistoma vannamei . The complete structure of PFD was determined by a detailed NMR analysis, including 1 H- 13 C and 1 H- 15 N-HBMC data. In addition, conformational and DFT computational studies also were performed. A group of fishes ( n = 6) was treated orally with PFD (0.1, 0.5 and 1.0 mg/mL; 20 μL) and subjected to locomotor activity and light/dark tests, as well as, acute toxicity 96 h. The involvement of the GABAergic and serotonergic (5-HT) systems was investigated using flumazenil (a silent modulator of GABA receptor) and 5-HT 1 , 5-HT 2A/2C and 5-HTR 3A/3B receptors antagonists, known as pizotifen, granisetron and cyproheptadine, respectively. PFD was nontoxic, reduced locomotor activity and promoted the anxiolytic effect in zebrafish. Flumazenil did not inhibit the anxiolytic effect of the PFD via the GABAergic system. This effect was reduced by a pretreatment with pizotifen and granisetron, and was not reversed after treatment with cyproheptadine. Molecular docking and dynamics studies confirmed the interaction of PFD with the 5-HT receptor.Communicated by Ramaswamy H. Sarma. |
