Complexos de platina(II), paládio(II) e ouro(I) com aril-tiossemicarbazonas: investigações em química de coordenação e química medicinal

Abstract

Cancer is considered one of the main causes of death around the world. This disease can be treated using radiotherapy, surgery, and chemotherapy. The development of novel compounds which are more active and less toxic and which could eventually become antitumor drugs constitutes a research area of great relevance. Since the discovery of the anticancer activity of cisplatin, studies involving the use of metal complexes as drugs have grown substantially. Aiming to improve the spectrum of antitumor activity, decrease side effects and cellular resistance, the development of new metallic complexes is considered of great importance. The coordination chemistry of thiosemicarbazones has great interest considering their variable donor ability, structural diversity and biological applications. Besides anticancer activity, some thiosemicarbazones have been used in the development of antibacterial drugs, and others have demonstrated antiviral activity. Aiming to obtain novel platinum(II), palladium(II) and gold(I) complexes that exhibit biological activity, we have synthesized twenty four complexes using thiosemicarbazones as six ligands. The interactions between thiosemicarbazones and metal ions have been investigated due to the interest in their biological and chemical properties. Investigations have been conducted to identify the groups directly bound to the metal and the structure of the coordination compounds formed. The novel complexes that were developed have been characterized by elemental analyses, Raman, IR, NMR spectroscopy, mass spectrometry, TG/DTA and Cyclic Voltammetry. The cytotoxities of the compounds have been investigated against tumor cell lines (B16-F10 and CT26.WT) and non-tumor cell line (BHK-21). Some of the studied complexes have shown cytotoxicity comparable to or better than that of cisplatin, mainly gold complexes with triphenylphosphine. The antibacterial activities of the compounds have been assayed against Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica subsp. entérica serovar Typhimurium e Escherichia coli. Coordination to metallic ion has proven to be a good strategy for improving the antibacterial activity, especially for the gold(I) complexes. All thiosemicarbazone and their respective gold(I) complexes were evaluated for their ability to inhibit the activity of the thioredoxin reductase (TrxR) enzyme. The non-substituted phosphines turned out to be effective inhibitors of TrxR at the lower concentration tested (5μM) when compared to the gold phosphine complexes. Both complexes, in most of the cases, were more efficient TrxR inhibitors than the ligands.