UM NOVO COMPOSTO DE COORDENAÇÃO DINUCLEAR PROJETADO PARA NÃO APRESENTAR DANOS OXIDATIVOS E EFEITOS TOXICOLÓGICOS

Abstract

A NEW DINUCLEAR COORDINATION COMPOUND DESIGNED TO HAVE NO OXIDATIVE DAMAGE AND TOXICOLOGICAL EFFECTS. The synthesis, characterization, acute toxicity, antitumor activity, and histopathological analysis of a novel dinuclear platinum(2+) complex − [Pt(DACH-κ2N)µ-(C4H2O6-κ4O)Pt(DACH-κ2N)] − is reported. Through acute toxicity tests, it was possible to place the platinum complexes into categories according to the OECD protocol. The dinuclear complex was classified in category 2 (cisplatin - category 1; and oxaliplatin - category 2). Analyzing the interaction between dsDNA and dinuclear complex was observed an Tm increase, suggesting that the dinuclear complex-dsDNA interact probably through of the interstrand form. Evaluations of tumor masses extracted from mice inoculated with Ehrlich carcinoma demonstrated a percent of tumor inhibition similar for cisplatin and oxaliplatin, but statistically different and superior for the case of the dinuclear complex. Cisplatin and oxaliplatin showed 41.4 and 40.8% inhibition, respectively, while the dinuclear complex presented 66.3%. The histopathological analysis demonstrated that the group treated with cisplatin showed more significant tissue damage, moderate hepatic steatosis, and nephritis. The livers, spleens, and kidneys of the animals treated with the dinuclear complex were within the normality range with no tissue lesions, and absence of metastasis.