Integrated quantum chemical calculations and in silico approach to the anxiolytic effects of campesterol and its derivatives, with evaluation of locomotor activity in adult zebrafish (Danio rerio)

Abstract

Abstract In this study, the anxiolytic and locomotor activity of campesterol and its seven derivatives were evaluated. The tests were analyzed using the zebrafish ( Danio rerio ) model. The animals were treated intraperitoneally ( i.p .) with the samples (4, 20, and 40 mg/kg in 20 µL) and subjected to locomotor activity and acute toxicity tests. They underwent locomotion analysis in the open field test and anxiolytic effect analysis in the light and dark test. The mechanism of action was analyzed using flumazenil as an antagonist for each sample tested. Among the computational predictions, DFT analyses were performed to evaluate the possible structural behavior of the respective campesterol derivatives. The biological analysis evaluated the possible mechanism of action focused on the interaction between ligand and protein through molecular docking simulations. As a result, the data provide insight into the pharmacological effect of these derivatives on ZFa. The data show motor impairment in ZFa with each campesterol derivative. The results also point to anxiolytic behavior in animals, as well as flumazenil, in the analysis performed with hydrogenated campesterol. Biological analyses demonstrate that the possible action via the GABAergic pathway reinforces the biological association through application at a site adjacent to the crystallized drug, evidencing the possible route of action of hydrogenated campesterol. New pharmacological evidence opens horizons for therapeutic approaches to be investigated.