Avaliação do potencial citotóxico e antibacteriano in vitro de complexos triazenido e benzotriazenido-ona de Au(I) e Cu(II)

Abstract

Nowadays, the neoplastic diseases and bacterial infections caused by multidrug-resistant (MDR) microorganisms are ascending worldwide, representing great problems to public health. Thus, new antitumor and antimicrobial agents have been largely investigated. In this regard, metallodrugs open an array of possibilities, which traditional organic molecules cannot fulfill any longer due to growing drug resistance. For this reason, the present study aimed to evaluate the in vitro biological potential of four new metal complexes containing gold(I) or copper(II) íons: [(L)Au(PPh3)], where PPh3 = triphenylphosphane and HL = 1-(4-amidophenyl)-3-(4-acetylphenyl)triazene; [(L)2(Py)2(OH2)Cu(II)], [(bipy)2(L)4Cu(II)2] and [(Phen)2(L)4Cu(II)2], where Py = pyridine; bipy = 2,2’-bipyridine, phen = 1,10-phenanthroline and HL = 1,2,3-benzotriazine-4(3H)-one. So, after characterization by means of spectroscopic techniques and single-crystal X-ray diffraction, these compounds were evaluated for their cytotoxic (IC50 values – concentration that causes 50% inhibition in the cell growing compared to control) and antibacterial (MIC values – Minimal Inhibitory Concentration) in vitro activities. Cytotoxic effects of compounds on bone marrow cells from untreated patients with suspected hematological malignancies were investigated by cytotoxicity assay, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) as reagent. The antibacterial properties of these complexes against potentially pathogenic bacterial strains were evaluated by the Mueller-Hinton broth microdilution method. In addition, Cu(II) complexes were tested for their cytotoxix potential towards tumor cell lines (K562, MCF-7 and B16F10), as well as one non tumor cell (Vero) by MTT assay. The results obtained for [(L)Au(PPh3)] showed that this Au(I) triazenide complex was strongly cytotoxic on cells from patient with myelodysplastic syndrome (IC50 = 7.72 μM) and presented distinguished activity against Gram-positive bacterial strains, including MDR microorganisms. In turn, dinuclear Cu(II) complex containing phen co-ligands in coordination sphere [(Phen)2(L)4Cu(II)2] showed considerable cytotoxic effects on tumor cells (up to 16 times bigger than the one obtained to the metallodrug Cisplatin). This complex was highly cytotoxic on B16F10 melanoma (IC50 = 4.37 μM) and MCF-7 breast cancer (IC50 = 6.16 μM) lineages, as well as on bone marrow samples, especially from patients with chronic myeloid leukemia (IC50 = 7.76 μM) and myeloproliferative syndrome (IC50 = 7.01 μM). Remarkably, both Cu(II) complexes containing bipy or phen co-ligands presented antibacterial effects against Gram-positive and Gram-negative strains. Therefore, these findings clearly indicate that [(L)Au(PPh3)] and [(Phen)2(L)4Cu(II)2] have promising in vitro cytotoxic and antibacterial properties.