Efeito neuroprotetor do inibidor do transportador de prolina (LQFM164) em modelo animal de isquemia cerebral

Abstract

Introduction: Cerebral ischemia is a debilitating neurological condition associated with high rates of mortality and morbidity. This highlights the importance of studying new prototypes for treatment. Objective: To investigate the neuroprotective potential of the prototype LQFM164 (an inhibitor of the L-proline transporter PROT/SLC6A7) in an animal model of middle cerebral artery occlusion (MCAO), as well as the compound's pharmacokinetics and pharmacodynamics through in silico analyses. Methods: C57BL/6 mice were subjected to the MCAO model and treated with different doses (1.25 mg/kg, 2.5 mg/kg, and 5 mg/kg) for five days. Evaluations included molecular docking and molecular dynamics simulations, as well as motor assessments (Limb Clasping and Cylinder Test) and morphological analysis (TTC staining). Results and Discussions: The results indicate that LQFM164 significantly reduces the cerebral infarct area at doses of 2.5 mg/kg (9.33 ± 1.80%) and 5 mg/kg (4.70 ± 0.91%), and improves motor function in behavioral tests, suggesting a neuroprotection effect. Conclusion: The prototype LQFM164 demonstrated a neurorestorative effect in a territorial cerebral ischemia model, highlighting its potential as a promising candidate for future therapies in neurological disorders.