Síntese e avaliação da atividade biológica de complexos de platina e paládio com derivados da benzilpiperazina e do fenil-oxadiazol

Abstract

The study of platinum complexes for use in chemotherapy had a big impulse in the late 60’s with discovery of cisplatin [cis-diamminedichloridoplatinum(II)], it is useful for many types of cancer. However, its efficacy is limited by an emergency of cellular resistance and side effects, thus it has been search effective compounds for many cancers and to have less side effects. Thus, there is great interest in search for analogs and complexes containing other metals, for example palladium(II) that presents the coordination chemistry similar to the platinum(II). In this context this work describes the synthesis, characterization, cytotoxic activity, antibacterial activity and antiparasitic activity of platinum(II) and palladium(II) complexes with ligands derived from benzylpiperazine and phenyl-oxadiazole. The cytotoxicity of compounds was investigated in two tumor cell lines and one normal cell to determine cell viability (IC50). The antibacterial activity of complexes was evaluated for minimum inhibitory concentration (MIC), it was possible to observe the coordination favored the activity in some strains. It is knowing that many platinum(II) and palladium(II) complexes with diamines have shown good cytotoxic activity and the isomer 1,2,4-oxadiazole is present in compounds with known pharmacological action it was decided to synthesize complexes with diamines containing oxadiazole and others benzyl groups. The synthesized compounds were characterized by IV, Raman, RMN 1H, 13C and 195Pt, and CHN. Only compounds 3, 4 and 8 containig ligands derivatives from phenyl-oxadiazole containing platinum and NO2 in meta and CF3 in para and containing palladium and CF3, respectively, were able to inhibit in 50% the cellular viability in tumor cell lines without inhibit healthy cells growth, which shows selectivity. The antibacterial activity results of complexes 3, 4, 7 (containing NO2 in meta and palladium) and 8 deserves attention while the ligands do not present significant responses, which shows the importance of the metal ion, besides the active complexes were derived from ligands containing NO2 in meta position and CF3 in para as a substituent on aromatic ring, therefore they also contributed to the complex activity. Finally, was evaluated the antiparasitic activity, however only ligands B and C, NO2 derivatives, inhibited the parasite.