Estudo de complexos metálicos de RuII, NiII, PdII e PtII com ligantes aciltioureias: atividade citotóxica e interação com biomoléculas

Abstract

In this work, two series of phosphine complexes containing acylthiourea ligands were synthesized, characterizatied and evaluatied of the cytotoxic activities. The first series of compounds was composed of complexes with the general formula [RuLn (bipy) (P-P)] PF6, where Ln = N ', N'-dimethyl-N-benzoyl thiourea (L1), N', N'-dimethyl-N-thiophenyl thiourea (L2) or N ', N'-dimethyl-N-furoyl thiourea (L3); bipy = 2,2'-bipyridine and P-P: 1,2-bis (diphenylphosphine) ethane (dppe) or 1,4-bis (diphenylphosphine) butane (dppb) and the second series of complexes with the formula [MLn(dppe)]BF4, where M = NiII, PdII or PtII. The complexes were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance (31P{1H}, 1H and 13C{1H}, COSY, HMBC and HSQC), cyclic voltammetry and X-ray diffraction. The cytotoxic activity of the complexes against breast (MDA-MB-231 (tumor); MCF-7 (tumor); MCF-10A (non-tumor)) and lung (A549 (tumor); MRC-5 (non-tumor)) tumor and non tumor cell lines was performed by MTT assay. The first series of complexes showed activity and selectivity for all tumor lines evaluated, while the second series of complexes showed better results in breast tumor cell lines. The complexes of series 1 (3 and 6) and 2 (8, 10 and 12) when evaluated in the breast tumor line (MDA-MB-231) inhibited colony formation, altered morphology and inhibited cell migration from the Wound Healing assay. Still in the same breast tumor lineage, they led to an accumulation of cells in Sub-G1 phase on cell cycle analysis. The compounds 3 and 6 induced cell death by apoptosis. All complexes shown weak reversible interactions via minor groove of CT-DNA and the series 1 complexes interacted with the HSA protein.