Novos complexos de paládio(II) contendo tiossemicarbazonas: citotoxicidade, estudos de interação com proteínas e avaliação do potencial antitumoral
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Data
2019-12-12
Autores
Lazzarini, Ana Beatriz
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer é a segunda doença mais fatal e onera em US$1,16 trilhão/ano. Seu tratamento tem como base os quimioterápicos baseados em platina(II), em destaque, a cisplatina. Em contrapartida aos seus benefícios, tais compostos apresentam baixa seletividade e resultam em diversos efeitos colaterais. Dentre os metais mais promissores no desenvolvimento de novos metalofármacos, encontram-se os compostos baseados em paládio(II). Neste trabalho, foram sintetizados e caracterizados quatro complexos metálicos (AB1-4) de fórmula geral [Pd(TSC)PPh3X], sendo X = Cl-, I-, SCN-, N3-; PPh3 = trifenilfosfina e TSC = tiossemicarbazona. Uma vez que os compostos AB1 e AB4 apresentaram significativo grau de pureza, foram avaliadas as suas respectivas interações com o DNA e a albumina do soro humano (HSA). O composto AB1 apresentou interação com ambas biomoléculas, suprimindo 77% da fluorescência da albumina e apresentando uma constante de ligação equivalente a 2,29x104 M-1 com o DNA, levando à hipótese de a mesma ocorrer via os sulcos do DNA. Já o composto AB4 suprimiu 74% da fluorescência da albumina e não apresentou interação com o DNA. Uma vez que o composto AB1 mostrou ser mais promissor, realizou-se o teste de viabilidade celular para as linhagens humanas MCF-7 (célula tumoral mamária), A549 (célula tumoral pulmonar) e MRC5 (célula pulmonar sadia). Os resultados indicam que o complexo apresenta atividade antiproliferativa superior à cisplatina para a linhagem mamária (IC50 AB1 = 6,48 µM; IC50 cisplatina > 50 µM) e equivalente para a linhagem pulmonar (IC50 AB1 = 4,52 µM; IC50 cisplatina = 4,97 µM).
Cancer is currently the second most fatal disease, with its management amounting to US$1,16 trillion/year. Treatment of a significant number of cancers is based on platinum(II) compounds, especially cisplatin. In contrast to their benefits, such compounds exhibit low selectivity and lead to various side effects. Among the metals palladium(II) compounds are believed to be the most promising alternative to platinum-based drugs. In this study, four metal complexes (AB1-4) with the general formula [Pd(TSC)PPh3X] were synthesized and characterized, in which X = Cl-, I-, SCN-, N3-; PPh3 = triphenylphosphine, and TSC = thiosemicarbazone. Since compounds AB1 and AB4 presented high levels of purity, their respective interactions with DNA and human serum albumin (HSA) were evaluated. AB1 interacted with both biomolecules, quenching 77% of HSA fluorescence and showing a binding constant equivalent to 2,29x104 M-with DNA, which suggests that the process may involve DNA grooves. On the other hand, while AB4 quenched 74% of HSA fluorescence, it did not exhibit interactions with DNA. Given AB1’s higher biomolecule-binding abilities, the compound was tested in viability assays with the human cell lines MCF-7 (breast cancer), A549 (lung cancer) and MRC5 (healthy lung, control cells). The results showed that AB1 presented antiproliferative activity higher than cisplatin in MCF-7 cells (IC50 AB1 = 6,48 µM; IC50 cisplatina > 50 µM) and equivalent to cisplatin in A549 cells (IC50 AB1 = 4,52 µM; IC50 cisplatina = 4,97 µM).
Cancer is currently the second most fatal disease, with its management amounting to US$1,16 trillion/year. Treatment of a significant number of cancers is based on platinum(II) compounds, especially cisplatin. In contrast to their benefits, such compounds exhibit low selectivity and lead to various side effects. Among the metals palladium(II) compounds are believed to be the most promising alternative to platinum-based drugs. In this study, four metal complexes (AB1-4) with the general formula [Pd(TSC)PPh3X] were synthesized and characterized, in which X = Cl-, I-, SCN-, N3-; PPh3 = triphenylphosphine, and TSC = thiosemicarbazone. Since compounds AB1 and AB4 presented high levels of purity, their respective interactions with DNA and human serum albumin (HSA) were evaluated. AB1 interacted with both biomolecules, quenching 77% of HSA fluorescence and showing a binding constant equivalent to 2,29x104 M-with DNA, which suggests that the process may involve DNA grooves. On the other hand, while AB4 quenched 74% of HSA fluorescence, it did not exhibit interactions with DNA. Given AB1’s higher biomolecule-binding abilities, the compound was tested in viability assays with the human cell lines MCF-7 (breast cancer), A549 (lung cancer) and MRC5 (healthy lung, control cells). The results showed that AB1 presented antiproliferative activity higher than cisplatin in MCF-7 cells (IC50 AB1 = 6,48 µM; IC50 cisplatina > 50 µM) and equivalent to cisplatin in A549 cells (IC50 AB1 = 4,52 µM; IC50 cisplatina = 4,97 µM).
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Palavras-chave
Câncer, Complexos de paládio(II), Atividade biológica