Anxiolytic Effect of the Chalcone (2E)-1-(4′-aminophenyl)-3-furan-2-yl-prop-2-en-1-one in Adult Zebrafish ( Danio rerio ): Involvement of the 5-HT System

Abstract Chalcones constitute a relevant class of flavonoids with diverse pharmacological potential, including activity in the central nervous system. In this study, the anxiolytic potential of the chalcone (2E)-1-(4′-aminophenyl)-3-furan-2-yl-prop-2-en-1-one (CPAfurf) was investigated through in vivo and in silico assays using adult zebrafish (Danio rerio). Molecular docking studies revealed a significant affinity of CPAfurf for the serotonergic receptors 5-HT2A, 5-HT2C, and 5-HT3A, with interaction patterns similar to reference antagonists. In acute toxicity tests, the molecule showed no toxic effects at the evaluated doses (LD50 > 40 mg/kg). In behavioral assays, CPAfurf demonstrated a consistent anxiolytic effect, evidenced by an increased time spent in the light zone and greater exploration of the upper region of the tank, with minimal interference in locomotion at low concentrations. Furthermore, the anxiolytic effect was reversed by pretreatment with serotonergic antagonists, indicating the direct involvement of the 5-HT pathway, especially the 5-HT3A receptors. Taken together, the findings suggest that the chalcone CPAfurf presents potential as a serotonergic modulator and a promising bioactive compound candidate for the development of new anxiolytic agents with a reduced toxicity profile.