Anxiolytic-like effect of chalcone N-{4’[(2E)-3-(3-nitrophenyl)-1-(phenyl)prop-2-en-1-one]} acetamide on adult zebrafish (Danio rerio): Involvement of the 5-HT system

• Published in: Biochemical and biophysical research communications 2020-05, Vol.526 (2), p.505-511
• Main Authors: Ferreira, Maria Kueirislene Amâncio, da Silva, Antonio Wlisses, Silva, Francisca Crislândia Oliveira, Vieira Neto, Antônio Eufrásio, Campos, Adriana Rolim, Alves Rodrigues Santos, Sacha Aubrey, Rodrigues Teixeira, Alexandre Magno, da Cunha Xavier, Jayze, Bandeira, Paulo Nogueira, Sampaio Nogueira, Carlos Emídio, de Brito, Débora Hellen Almeida, Rebouças, Emanuela Lima, Magalhães, Francisco Ernani Alves, de Menezes, Jane Eire Silva Alencar, dos Santos, Hélcio Silva
• Format: Article
• Language: English
• Subjects: Acetamides - chemistry; Acetamides - pharmacology; Adult zebrafish; Animals; Anti-Anxiety Agents - chemistry; Anti-Anxiety Agents - pharmacology; Anxiety - drug therapy; Anxiety - metabolism; Anxiolytic-like effect; Chalcone; Chalcone - analogs & derivatives; Chalcone - pharmacology; Drug Discovery; Locomotion - drug effects; Molecular Docking Simulation; Receptors, Serotonin, 5-HT1 - metabolism; Serotonergic receptors; Serotonin - metabolism; Zebrafish; Zebrafish Proteins - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.03.129

The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4’-[(2E) -3- (3-nitrophenyl) -1- (phenyl) prop-2-en-1-one] acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies. [Display omitted] •The chalcona PAAPMNBA is not toxic and alters the locomotion of adult zebrafish.•PAAPMNBA reduced anxiety of the adult zebrafish model via serotonergic system.•PAAPMNBA tem affinity hair receptors 5-HTR1 and 5-HTR2A/2C.