Effect of Cinnamaldehyde Chalcone on Behavior in Adult Zebrafish (Danio rerio): In Silico Approach

• Published in: Chemistry & biodiversity 2024-08, Vol.21 (8), p.e202400935-n/a
• Main Authors: Carneiro Romão, Ivana, Costa Siqueira, Sônia Maria, Amâncio Ferreira, Maria Kueirislene, Wlisses da Silva, Antonio, Machado Marinho, Márcia, Ferreira Ribeiro, Walber Henrique, Castro Gomes, Andreia Ferreira, Alencar de Menezes, Jane Eire Silva, Santos, Hélcio Silva
• Format: Article
• Language: English
• Subjects: Acrolein - analogs & derivatives; Acrolein - chemistry; Acrolein - pharmacology; Animals; Anti-Anxiety Agents - chemical synthesis; Anti-Anxiety Agents - chemistry; Anti-Anxiety Agents - pharmacology; Anxiety; Aquariums; Behavior, Animal - drug effects; Benzodiazepines; Bioavailability; Chalcone; Chalcone - analogs & derivatives; Chalcone - chemistry; Chalcone - pharmacology; Chalcones - chemical synthesis; Chalcones - chemistry; Chalcones - pharmacology; Cinnamaldehyde; Coupling (molecular); Danio rerio; Diazepam; Flumazenil; GABAergic; Hepatotoxicity; Locomotion - drug effects; Locomotor activity; Molecular Docking Simulation; Molecular Structure; Pharmacology; Receptors; Receptors, GABA-A - metabolism; Structure-Activity Relationship; Virtual memory systems; Zebrafish; γ-Aminobutyric acid A receptors
• ISSN: 1612-1872; 1612-1880; 1612-1880
• DOI: 10.1002/cbdv.202400935

The study focuses on the anxiolytic potential of chalcone (2E,4E)‐1‐(2‐hydroxyphenyl)‐5‐phenylpenta‐2,4‐dien‐1‐one (CHALCNM) in adult zebrafish. Successfully synthesized in 58 % yield, CHALCNM demonstrated no toxicity after 96 h of exposure. In behavioral tests, CHALCNM (40 mg/kg) reduced locomotor activity and promoted less anxious behavior in zebrafish, confirmed by increased permanence in the light zone of the aquarium. Flumazenil reversed its anxiolytic effect, indicating interaction with GABAA receptors. Furthermore, CHALCNM (4 and 20 mg/kg) preserved zebrafish memory in inhibitory avoidance tests. Virtual screening and ADMET profile studies suggest high oral bioavailability, access to the CNS, favored by low topological polarity (TPSA≤75 Å2) and low incidence of hepatotoxicity, standing out as a promising pharmacological agent against the GABAergic system. In molecular coupling, CHALCNM demonstrated superior affinity to diazepam for the GABAA receptor. These results reinforce the therapeutic potential of CHALCNM in the treatment of anxiety, highlighting its possible future clinical application.