Navegando por Autor "Moura, Severino Vitor do Nascimento"

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    Síntese, caracterização e estudo citotóxico de um metaloprotótipo à base de rutênio 3+) com potencial atividade antileucêmica
    (2024-07-29) Moura, Severino Vitor do Nascimento; Silva, Wagner Eduardo da; Belian, Mônica Freire; http://lattes.cnpq.br/2626644337183959; http://lattes.cnpq.br/8612340815622413; http://lattes.cnpq.br/0613129512420118
    Ruthenium complexes constitute a promising class of metalloprototypes due to their biological activities. These ruthenium-based complexes have peculiar characteristics such as low associated toxicity, effective lability rate and “selectivity” to cancer cells, promoting damage to nuclear nDNA and apoptosis. Using strategies in combination with the Ru3+ ion and ligands with bioactive activities, the complex formed can show enhanced biological responses. This study aimed to synthesize, characterize and study the cytotoxicity of a metalloprototype containing ruthenium and ascorbate as a ligand. The synthetic methodology used enabled the formation of sodium ascorbate from the deprotonation of ascorbic acid with sodium bicarbonate in water, guaranteeing a reaction yield of 83%. The synthesized sodium ascorbate was then reacted with ruthenium (3+) chloride in water for 12 hours, resulting in the formation of the compound with the minimum formula [Ru(Asc)(OH2)4]Cl2 in a yield of 85%. This form was characterized by spectroscopy at infrared wavelengths, with significant differences in the absorption coefficients, such as the C=O and C=C bonds, when compared to ascorbic acid. The [Ru(Asc)(OH2)4]Cl2 complex was characterized by infrared spectroscopy, suggesting its formation through the shifts observed in the absorption bands of the C=O, C=C and C-O bonds. The characterization of the complex by electronic absorption spectroscopy showed hypsochromic shifts of the transitions located in the ligand of the π→π* type and the presence, in the visible, of transitions of the d→d type. The 1H NMR spectrum of the complex showed three signals, the multiplicities of which were two doublets and one triplet, the 13C NMR spectrum showed six signals consistent with the structure of the ligand used and the HSQC NMR spectrum showed three C-H correlation signals, also consistent with the complex studied. The high-resolution mass spectrum of the [Ru(Asc)(OH2)4]Cl2 complex showed six signals for the ruthenium isotopes (98Ru, 99Ru, 100Ru, 101Ru, 102Ru and 104Ru) with the highest relative m/z of 278.75, referring to the presence of Ru3+ and the ascorbate ligand [C6H9O6102Ru]+. The results of the cytotoxicity tests of the [Ru(Asc)(OH2)4]Cl2 complex, carried out on RAW 264.7 (normal cell line), MCF-7 (breast cancer) and HL-60 (human leukemia) cells, showed cytotoxic activity for the HL-60 cell line, with an IC50 of 39.3 μmol.L-1. For the normal cell line, the ruthenium complex proved to be non-cytotoxic (IC50 60.0 μmol.L-1). Therefore, the synthetic strategies used were satisfactory, with yields above 80%. The characterization techniques used were consistent with the formation of the complex obtained. The in vitro toxicological test showed evidence of non-toxicity to healthy cells and proved to be active in human leukemia cells (HL-60), possibly acting as an anti-leukemia candidate.