Chalcone Derived from a Natural Product: An Integrated Approach of Quantum Chemical Calculations, Molecular Docking, ADME and Neuromodulation on Serotonergic Receptors in Adult Zebrafish

Priscilla Teixeira da Silva; Maria Kueirislene Amâncio Ferreira; Roberto Lima de Albuquerque; Alexandre Magno Rodrigues Teixeira; Emmanuel Silva Marinho; Márcia Machado Marinho; Jesyka Macedo Guedes; Marisa Jádna Silva Frederico; Andreia Ferreira de Castro Gomes; Jane Eire Silva Alencar de Menezes; Hélcio Silva dos Santos

doi:10.29169/1927-5951.2025.15.07

Chalcone Derived from a Natural Product: An Integrated Approach of Quantum Chemical Calculations, Molecular Docking, ADME and Neuromodulation on Serotonergic Receptors in Adult Zebrafish

Authors

Priscilla Teixeira da Silva Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil
Maria Kueirislene Amâncio Ferreira State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil
Roberto Lima de Albuquerque State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil
Alexandre Magno Rodrigues Teixeira State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil
Emmanuel Silva Marinho State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil
Márcia Machado Marinho State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil
Jesyka Macedo Guedes State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil
Marisa Jádna Silva Frederico Department of Pharmacology and Physiology, Center for Drug Research and Development, School of Medicine, Federal University of Ceará
Andreia Ferreira de Castro Gomes Center for Molecular and Environmental Biology, University of Minho, School of Sciences, Department of Biology, Braga, Portugal
Jane Eire Silva Alencar de Menezes State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil
Hélcio Silva dos Santos Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil; State University of Ceara, Graduate Program in Natural Sciences, Fortaleza, CE, Brazil and State University of Vale do Acaraú, Chemistry Course, Sobral, CE, Brazil

DOI:

https://doi.org/10.29169/1927-5951.2025.15.07

Keywords:

Chalcones, Anxiolytic effect, Serotonergic receptors, Zebrafish

Abstract

Anxiety disorders are conditions characterized by heightened responses to perceived threats, resulting in symptoms that negatively affect everyday life. This study investigates the anxiolytic effect of a natural chalcone isolated from Croton anisodontus Müll.Arg. focusing on its modulation of anxiolytic activity in modulating anxiolytic activity via GABAergic and serotonergic neurotransmission in an adult zebrafish model. The acute toxicity of the chalcone was assessed during a 96-hour period, and the anxiolytic behavior of fish treated with chalcone was evaluated using light/dark tests and open field tests (n=6 animals per group). Chalcone showed no signs of toxicity for up to 96 hours of analysis. The results demonstrated a significant anxiolytic effect of the synthesized chalcone, suggesting its therapeutic potential in treating anxiety. Furthermore, the findings indicate that this anxiolytic effect is mediated by serotonergic and non-GABAergic neurotransmitter systems. From molecular docking simulations, it was possible to estimate that the 5-HT3A receptor (5-HT3AR) pathway is the most likely target way for the chalcone to act. MPO-based ADME predictions indicate that the chalcone exhibits high cellular permeability suggest that chalcone has a high cellular permeability and can distribute better in biological tissues than in blood plasma, supporting its potential to act in the CNS by crossing the blood-brain barrier. These findings enhance the understanding of contribute to understanding of chalcone's mechanisms of action and provide a solid basis for future studies aimed at developing new therapeutic strategies to develop new therapeutic approaches for anxiety disorders.

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