Avaliação de efeitos citotóxicos de um novo complexo de rutênio “Ru-Naftil” em modelo celular de câncer de próstata metastático

Abstract

Prostate cancer remains one of the leading causes of cancer-related mortality among men worldwide, particularly in advanced stages such as metastatic castration-resistant prostate cancer, where resistance to hormonal therapy and limited chemotherapy efficacy compromise clinical outcomes. Ruthenium-based compounds have emerged as promising alternatives to conventional chemotherapy because of their distinct mechanisms of action and improved tumor selectivity. In this study, a novel ruthenium(II)-β-diketonate complex, cis-[Ru(tfnb)(dppm)₂]PF₆ (Ru-Naphthyl), was synthesized in good yield and fully characterized by elemental analysis, Fourier-transform infrared spectroscopy, multinuclear nuclear magnetic resonance spectroscopy, and high-resolution electrospray ionization mass spectrometry, confirming the proposed structure. The complex exhibited selective cytotoxicity toward PC-3 prostate cancer cells, with an IC₅₀ value of 14.19 μM, whereas lower toxicity was observed in non-tumoral PNT-2 cells (IC₅₀ = 34.85 μM), resulting in a selectivity index of 2.46. In contrast, neither the non-coordinated ligand nor the ruthenium precursor showed significant cytotoxic activity under the same experimental conditions. Furthermore, the complex markedly reduced clonogenic survival and promoted intracellular reactive oxygen species accumulation, predominantly in tumor cells. Oxidative stress may have been associated with disruption of cell cycle progression, evidenced by a reduced G2/M population and increased sub-G1 events, culminating in apoptotic cell death. Collectively, these findings demonstrate that Ru-Naphthyl exhibits promising antitumor activity against prostate cancer cells through oxidative stress-mediated mechanisms and supports further investigations to elucidate its molecular targets and evaluate its therapeutic potential.