Avaliação do possível efeito ansiolítico-símile do composto (Z)-N’-(1-benzil-2-oxoindolin-3-ilideno)-2-fluor-benzodrazida por meio de estudos in silico, in vivo e in vitro

Abstract

Anxiety disorders constitute a relevant public health problem, characterized by high prevalence and important therapeutic limitations, which justifies the prospecting of new pharmacological alternatives. The present study aimed to evaluate the possible anxiolytic-like effect of the compound (Z)-N’-(1-benzyl-2-oxoindolin-3-ylidene)-2-fluorobenzhydrazide (ISA) through in silico, in vivo, and in vitro approaches. In silico analyses indicated that the compound presents stable interactions with serotonergic receptors 5-HT1A, 5-HT2A, and 5-HT3A. In the in vivo studies, ISA promoted an anxiolytic-like effect in the Elevated Plus Maze, evidenced by an increase in the number of entries and the time spent in the open arms; this effect was partially reversed in the presence of flumazenil, an antagonist of GABAA receptors. In the Open Field and Rota Rod tests, the compound did not alter locomotor activity and motor coordination of the animals, respectively. In the experimental model of anxiety induced by pentylenetetrazol (PTZ), pretreatment with the compound was able to prevent anxiety-like behavior in the tested animals. Finally, the in vitro assays demonstrated that the compound was able to increase hippocampal GSH concentration in mice subjected to the experimental model of anxiety induction, in addition to showing low toxicity in glial cell culture. Taken together, the results suggest that the compound may interact satisfactorily with serotonergic receptors involved in the neurobiology of anxiety disorders. Furthermore, ISA showed an anxiolytic-like effect that appears to involve, at least in part, the GABAA receptor, without causing impairments in locomotor activity or motor coordination, at the doses and administration routes used. Finally, ISA showed an antioxidant effect related to increased GSH production in hippocampal homogenates and low toxicity in glial cell culture.