Synthetic Aminochalcone Prevents Hyperglycemia-Induced Anxiety and Delays Pentylenetetrazole-Induced Epileptic Crisis in Adult Zebrafish

Neurological disorders are a major contributor to disability-adjusted life years (DALYs) worldwide, with anxiety and epilepsy being particularly prevalent. Among them, anxiety is among the top ten diseases and causes an annual cost of 42.3 billion dollars in the United States. It can also increase the chance of developing diabetes, regardless of cardiometabolic and sociodemographic factors. Diabetes, if left uncontrolled for long periods, can lead to serious health problems and, in 2021, was responsible for the deaths of 1.6 million people and affected around 10.5% of the world population. chalcones belong to the class of flavonoid compounds and have gained prominence in recent years for presenting a wide range of physiological effects, with similar effects also being found in the literature when these compounds are synthesized. Therefore, the work aimed at the synthesis, characterization, toxicological, anxiolytic, hypoglycemic, and anticonvulsant analysis of the compound 4AAF in <i><i>Danio rerio</i>.</i> Initially, amino chalcone was synthesized employing the Claisen-Schmidt condensation reaction, and then its toxicity was tested over 96 h at concentrations of 0.1, 0.5, and 1.0 mg/mL. Subsequently, groups of 6 treated animals were formed to evaluate their effects in the following tests: light and dark, novel tank test, open field test, spinning task, anxiolytic action mechanism via GABA and serotonergic, chronic hyperglycemia, reactive oxygen species, and pentylenetetrazol-induced seizure. The compound produced was shown to be nontoxic, and anxiety tests were promising at concentrations of 0.5 mg/mL, showing that aminochalcone acts on both the GABA and serotonergic pathways and that it causes a reduction in the locomotor pattern of the animals. In the context of hyperglycemia, the concentration of 0.5 mg/mL significantly reduced blood glucose levels and oxidative stress in the liver, in addition to causing anxiolytic and sedative behavior. In the seizure test, the 1.0 mg/mL concentration partially reversed PTZ-induced convulsive behavior in stage three. Finally, synthetic chalcones have more than one physiological effect, requiring bioprospecting for other possible actions, and zebrafish become an interesting model to investigate their various uses.