Estudo integrado do potencial ansiolítico-símile e neuroprotetor do derivado tiofênico 6CN07 : abordagens in silico, in vivo e in vitro

Abstract

Anxiety disorders represent a significant public health challenge, and despite the diversity of anxiolytic drugs available, treatment remains limited by unsatisfactory clinical responses and adverse effects that compromise patient adherence. These factors highlight the urgent need to investigate new compounds with more effective and safer pharmacological profiles. In this context, the present study aimed to investigate the anxiolytic-like potential of the thiophene derivative 6CN07 and its possible mechanism of action through in silico, in vivo, and in vitro approaches. In silico analyses indicated that 6CN07 presented physicochemical and pharmacokinetic properties compatible with central nervous system-acting drugs, in addition to favorable interactions with key targets involved in the neurobiology of anxiety, namely 5 -HT1A, 5-HT2A, and GABA receptors. Regarding in vivo methodologies, 6CN07 promoted anxiolytic-like effects in mice subjected to the Elevated Plus Maze (EPM) and Light-Dark Box (LDB) tests, without inducing impairment in locomotor activity or motor coordination. Pharmacological antagonism studies indicated the possible involvement of GABAA and 5-HT2A receptors in the compound's effect. Additionally, 6CN07 exhibited an anxiolytic-like effect in the pentylenetetrazol (PTZ)-induced anxiety model and attenuated the oxidative stress associated with this model. Finally, in vitro analyses performed on astrocyte cultures in the presence of glutamate showed that 6CN07 preserved cell viability against glutamatergic excitotoxicity, suggesting a potential neuroprotective effect. Taken together, these results suggest that compound 6CN07 possesses a pharmacokinetic and physicochemical profile compatible with anxiolytic drugs, whose mechanism of action appears to involve GABAergic and serotonergic neurotransmission, attenuation of oxidative stress, and neuroprotection against glutamatergic excitotoxicity. However, further studies at the molecular level are necessary for a better understanding of this thiophene derivative's effects.