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Estudo do efeito de polioxometalatos com propriedades antibacterianas
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Abstract(s)
A permanente ocorrência de multirresistências bacterianas, nomeadamente por bactérias resistentes a antibióticos de última geração, aumenta a necessidade de encontrar novos compostos antibacterianos. Os polioxometalatos (POMs) são aglomerados de oxometalatos de metais de transição, particularmente molibdénio (Mo), tungsténio (W) e vanádio (V) que apresentam atividade antibacteriana. Os POMs puros, híbridos e nanopartículas contendo POMs apresentam atividades antibacterianas cada vez mais específicas e promissoras e por isso têm sido considerados como potenciais fármacos do futuro no tratamento de infeções bacterianas. Emboras os mecanismos de ação dos POMs não sejam totalmente conhecidos, as proteínas de membrana constituem potenciais alvos de ação. Na presente dissertação, analisou-se pela primeira vez o efeito de um polioxotungstato (POT) do tipo Preyssler ([NaP5W30O110]-14, abreviado de P5W30) na atividade da Ca2+-ATPase, bem como no crescimento de bactérias Gram positivas e Gram negativas, algumas das quais multirresistentes. Verificou-se que o P5W30 inibe a atividade da Ca2+-ATPase (IC50 0,4 μM) sendo um dos mais potentes inibidores até agora referidos. O P5W30 apresenta um tipo de inibição mista para esta ATPase. Os efeitos de P5W30 contra bactérias Gram negativas e Gram positivas foram analisados verificando-se que afeta fortemente as Gram positivas. Adicionalmente, analisou-se ainda combinações do composto P5W30 com os antibióticos cefoxitina, vancomicina e cloranfenicol contra a bactéria MRSA 16. Verificou-se um efeito sinérgico com o antibiótico cefoxitina. Observou-se ainda, pela primeira vez, um efeito sinérgico entre um POT e o antibiótico cloranfenicol ao reverter a resistência da bactéria MRSA 16 a este antibiótico.
Em conclusão, verificou-se que o composto P5W30 inibe fortemente a Ca2+-ATPase interagindo com a enzima em outro local para além do local ativo. O P5W30 apresenta potencial antibacteriano e ação sinérgica com antibióticos contra bactérias multirresistentes. Sugere-se uma potencial aplicação deste polioxometalato como futuro agente no combate contra bactérias multirresistentes.
The continued occurrence of bacterial multidrug resistance, increases the need to find new antibacterial compounds. Polyoxometalates (POMs) are metal oxide clusters of transition metals, particularly molybdenum (Mo), tungsten (W) and vanadium (V) that exhibit antibacterial activity. Pure, hybrid and nanoparticle POMs containing POMs have increasingly specific and promising antibacterial activities and have therefore been considered as potential future drugs in the treatment of bacterial infections. The POMs’ mechanisms of action remain unclear, however, membrane proteins are potential targets. In the present dissertation, the effect of a Preyssler-type polyoxotungstate (POT) ([NaP5W30O110]-14) (abbreviated P5W30) on Ca2+-ATPase activity as well as on the growth of collection and clinical multiresistant Gram positive and Gram negative bacteria was first analyzed. P5W30 has been found to inhibit Ca2+-ATPase activity (IC50 0,4 μM), being one of the most potent inhibitors so far reported. P5W30 has a mixed inhibition type for this ATPase. The effects of P5W30 against various bacteria, was analyzed and was found more active against Gram positive bacteria. Furthermore, combinations of compound P5W30 with the antibiotics cefoxitin, vancomycin and chloramphenicol against the bacterium MRSA 16 were also evaluated. A synergistic effect was observed with the antibiotic cefoxitin. A synergistic effect was also observed for the first time between a POT and chloramphenicol by reversing the resistance of the strain MRSA 16 to this antibiotic. In conclusion, it was found that the compound P5W30 inhibits Ca2+-ATPase by interacting with the enzyme at a site other than the active one. It also has individual antibacterial potential and synergistic action in combination with antibiotics against multidrug resistant bacteria. A potential application of this POT as a future agent against multidrug resistant bacteria is also suggested.
The continued occurrence of bacterial multidrug resistance, increases the need to find new antibacterial compounds. Polyoxometalates (POMs) are metal oxide clusters of transition metals, particularly molybdenum (Mo), tungsten (W) and vanadium (V) that exhibit antibacterial activity. Pure, hybrid and nanoparticle POMs containing POMs have increasingly specific and promising antibacterial activities and have therefore been considered as potential future drugs in the treatment of bacterial infections. The POMs’ mechanisms of action remain unclear, however, membrane proteins are potential targets. In the present dissertation, the effect of a Preyssler-type polyoxotungstate (POT) ([NaP5W30O110]-14) (abbreviated P5W30) on Ca2+-ATPase activity as well as on the growth of collection and clinical multiresistant Gram positive and Gram negative bacteria was first analyzed. P5W30 has been found to inhibit Ca2+-ATPase activity (IC50 0,4 μM), being one of the most potent inhibitors so far reported. P5W30 has a mixed inhibition type for this ATPase. The effects of P5W30 against various bacteria, was analyzed and was found more active against Gram positive bacteria. Furthermore, combinations of compound P5W30 with the antibiotics cefoxitin, vancomycin and chloramphenicol against the bacterium MRSA 16 were also evaluated. A synergistic effect was observed with the antibiotic cefoxitin. A synergistic effect was also observed for the first time between a POT and chloramphenicol by reversing the resistance of the strain MRSA 16 to this antibiotic. In conclusion, it was found that the compound P5W30 inhibits Ca2+-ATPase by interacting with the enzyme at a site other than the active one. It also has individual antibacterial potential and synergistic action in combination with antibiotics against multidrug resistant bacteria. A potential application of this POT as a future agent against multidrug resistant bacteria is also suggested.
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Keywords
Polioxometalatos Ca2+-ATPase Antibacterianos Multirresistências