Síntese, caracterização e avaliação das propriedades ansiolíticas do complexo de paládio(II) derivado do Bromazepam

Abstract

Anxiety disorders (ADs) constitute one of the most common mental disorders and are characterized by anxiety, which is a fundamental psychological condition of life, pathological. TAs negatively affect the life of an individual and of the people with whom he lives, damaging the performance of everyday activities and social relationships. Even though there are some classes of anxiolytics in the clinic, many patients are relapsed or nonresponsive. In this scenario, the aim of this work was to synthesize, characterize and evaluate the anxiolytic properties of [{2- (7-Bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-yl) 2-N, N-chloropalladium(II)], [(BMZ)PdCl2]. In this sense, the synthesis of the palladium (II) complex derived from bromazepam was performed with satisfactory yield, 75%. To understand the chemistry of the ligand as well as the complex obtained, two characterization techniques were used in which the ligand and the complex were subjected toNMR of 13C, 1H and HSQC analyzes. In addition, the complex was also characterized by the infrared (IR) technique and mass spectrometry coupled to gas chromatography (GC-MS). The results obtained from the NMR allowed to infer that the complex presented monomeric structure; the N4 and the pyridine N13 of the linker are the atoms that coordinate with the Pd(II). The IR allowed the detection of frequencies of stretches characteristic of the binder found also in the complex. The MS revealed the fragments of the complex. Regarding the anxiolytic activity, it was observed that the complex at the lowest dose (0.5 μg/kg) presented a significant reduction in the anxiety of the mice subjected to the plus maze test in relation to the control group (saline group), without causing alteration of the locomotor activity, and the analysis of the motor activity was also confirmed by the open field test. Likewise, it was possible to determine that the anxiolytic action of the complex occurs via GABAA receptor, since the animals that received pre-treatment with flumazenil and were treated with the complex did not present anxiolytic activity. Thus, the present study demonstrated that the [(BMZ)PdCl2] complex proved promising to the anxiolytic action, thus motivating those in the Catalysis and Chemical Reactivity Group (GCaR, Grupo de Catálise e Reatividade Química, em português) to seek a better understanding of this complex and probable analogs in the treatment of anxiety disorders.