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Biological Effects of Selenium-Containing Ionic Liquids: Cytotoxicity, Mercury Interaction, and Antiproliferative
Guilherme Schmitt Rieder1, Alessandro de Souza Prestes2, Fernanda D'Avila da Silva3
1Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
Abstract:
Selenium (Se) is an essential micronutrient that participates in redox regulation and cellular homeostasis. Selenium-containing ionic liquids (ILsSe) have emerged as hybrid compounds combining the properties of organoselenium molecules with the tunable features of ionic liquids. In this study, we evaluated the cytotoxicity, interaction with mercury (Hg2+), pharmacokinetic profile, and antiproliferative activity of three ILsSe (C1, C2, and C3). Human peripheral blood mononuclear cells (PBMCs) were used to assess cytotoxicity, showing that ILsSe were generally well tolerated at low micromolar concentrations, although their effects were dependent on exposure time and dose. The interaction of ILsSe with Hg2+ was investigated using a thiol oxidase assay, with diphenyl diselenide (DPDS) as a reference compound. The results indicate that ILsSe can interact with Hg2+, likely through the formation of Se-Hg species. In parallel, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis suggested that these compounds have physicochemical properties compatible with central nervous system exposure, including predicted blood-brain barrier permeability. In U87-MG glioblastoma cells, compound C3 exhibited concentration and time-dependent antiproliferative effects at low micromolar concentrations. These effects were associated with alterations in redox homeostasis, modulation of cell cycle progression, and induction of late-stage cell death. In general, ILsSe are biologically active compounds whose effects depend on dose and exposure time, warranting further investigation to clarify their toxicological profile and mechanisms of action. This study highlights the importance and biological potential of selenium-containing compounds.