Atividades biológicas de um complexo de cobre(II) contendo β-dicetona e 1,10-fenantrolina: citotoxicidade, genotoxicidade, toxicidade aguda e propriedade antitumoral

Abstract

The use of metal compounds as therapeutic drugs has gained prominence since the discovery of cisplatin. In the attempt to find save and more effective drugs, several metal based-drugs have been synthesized as potential antitumor agents. The use of the essential metals is justified because they are present in living organisms, participating in various biological processes. Among the trace elements it´s found the copper, which is considered an active redox metal that makes it possible the production of reactive oxygen species (ROS), which is considered its main function. In addition, copper is found at higher concentrations in tumor cells when compared to normal cells, which makes it an advantageous essential metal for new drugs development. Several studies have demonstrated that the complexation of copper with other ligands has provided the ability to cleave the DNA molecule, thus instigating the synthesis and characterization of new copper(II)-based complexes such as [Cu(BTA)phen]ClO4, evaluated in the present work. The [Cu(BTA)phen]ClO4 complex showed in vitro and in vivo antitumor activity. The mechanism of action of the complex is related to the redox reaction of the compound, which causes the production of ROS, aiding the direct or indirect action of the complex on the DNA, promoting the entrapment of the tumor cells in the G0/G1 phase and, consequently, inducting cell death. Evidences have shown that cell death is initiated by autophagy dysfunction, culminating in the induction of apoptosis. It was also observed that the complex under display selectivity to the tumor cells tested in vitro. Besides, in vivo assays showed that the complex possess potential antitumor, once that it reduce solid tumor volume in proportions very similar to cisplatin. It is noteworthy that the [Cu(BTA)phen]ClO4 complex presented lower toxicity during treatment when compared to cisplatin, which is evidenced by the weight loss observed in the cisplatin treated group. Therefore, the complex under study may be considered a promising antitumor agent.