Interação do glicopeptídeo Vancomicina em monocamadas de Langmuir como modelos de membrana celular
Data
2022-11-25
Autores
Santana, Heung Jin Alves 
Orientadores
Caseli, Luciano
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Fármacos com atividade microbicida, responsáveis por tratar adversidades causadas por infecções bacterianas, são amplamente utilizados no meio médico e clínico e devem envolver em seu mecanismo de ação interações com as membranas que limitam a bactéria. Este trabalho teve como objetivo analisar a interação do fármaco vancomicina (VC), utilizado amplamente para tratar infecções bacterianas, com modelos de membrana utilizando monocamadas de Langmuir constituídas de lipídios. Estes filmes foram formados pelos fosfolipídios dipalmitoilfosfatidilcolina (DPPC) e dipalmitoilfosfatidilserina (DPPS) para estudar os efeitos da vancomicina com modelo de membrana de eritrócitos, e os fosfolipídios dipalmitoilfosfatiletalonamina (DPPE) para estudar os efeitos do fármaco em modelos de camada externa de membranas citoplasmáticas de bactérias. VC foi incorporada à monocamada lipídica a partir da subfase aquosa, e a interação fármaco-lipídio foi analisada por isotermas de pressão e potencial de superfície-área, microscopia no ângulo de Brewster e espectroscopia no infravermelho. Para efeitos de comparação, realizou-se ensaios com o bioativo puro, com cada lipídio puro e com os filmes mistos de VC-DPPC, VC-DPPE e VC-DPPS. Para o DPPC, a VC condensou a monocamada, a deixando menos estável quando previamente comprimidas até altas pressões. Para o DPPE, a VC deixou o filme mais estável, sinalizando uma expansão da monocamada, além da formação de agregados. Por fim, a vancomicina condensou a monocamada de DPPS, interagindo com suas regiões hidrofílicas. Concluímos que a interação da vancomicina com os modelos de membrana na interface ar-água é modulada pela composição lipídica, e depende das interações intermoleculares com o grupo polar das moléculas formadoras da monocamada.
Drugs with microbicidal activity, responsible for treating adversities caused by bacterial infections, are widely used in the medical and clinical environment and must involve interactions with the membranes that limit the bacteria in their mechanism of action. Therefore, it is essential to understand, at a molecular level, the interaction of these substances with cell membranes. Thus, this work aimed to analyze the interaction of the drug vancomycin (VC), widely used to treat bacterial infections, with membrane models using Langmuir monolayers made up of lipids. These films were formed by the phospholipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS) to study the effects on an erythrocyte cell membrane, and the phospholipids dipalmitoylphosphatidylcholine (DPPE) to study the effects of the drug on outer layer models of bacterial cytoplasmic membranes. VC was incorporated into the lipid monolayer from the aqueous subphase, and the drug-lipid interaction was analyzed by surface pressure-area isotherms, surface potential-area isotherms, Brewster angle microscopy, and infrared spectroscopy. For comparison, tests were carried out with the pure bioactive, with each pure lipid, and with mixed films of VC-DPPC, VC-DPPE, and VC-DPPS. Vancomycin acted differently on each lipid studied. For DPPC, VC condensed the monolayer, making it less stable when previously compressed to high pressures. For DPPE, VC made the film more stable, signaling an expansion of the monolayer, in addition to the formation of aggregates. Finally, vancomycin condensed the DPPS monolayer, interacting with its hydrophilic regions. We conclude that the interaction of vancomycin with the membrane models at the air-water interface is modulated by the lipid composition and depends on the intermolecular interactions with the polar group of the molecules that form the monolayer.
Drugs with microbicidal activity, responsible for treating adversities caused by bacterial infections, are widely used in the medical and clinical environment and must involve interactions with the membranes that limit the bacteria in their mechanism of action. Therefore, it is essential to understand, at a molecular level, the interaction of these substances with cell membranes. Thus, this work aimed to analyze the interaction of the drug vancomycin (VC), widely used to treat bacterial infections, with membrane models using Langmuir monolayers made up of lipids. These films were formed by the phospholipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS) to study the effects on an erythrocyte cell membrane, and the phospholipids dipalmitoylphosphatidylcholine (DPPE) to study the effects of the drug on outer layer models of bacterial cytoplasmic membranes. VC was incorporated into the lipid monolayer from the aqueous subphase, and the drug-lipid interaction was analyzed by surface pressure-area isotherms, surface potential-area isotherms, Brewster angle microscopy, and infrared spectroscopy. For comparison, tests were carried out with the pure bioactive, with each pure lipid, and with mixed films of VC-DPPC, VC-DPPE, and VC-DPPS. Vancomycin acted differently on each lipid studied. For DPPC, VC condensed the monolayer, making it less stable when previously compressed to high pressures. For DPPE, VC made the film more stable, signaling an expansion of the monolayer, in addition to the formation of aggregates. Finally, vancomycin condensed the DPPS monolayer, interacting with its hydrophilic regions. We conclude that the interaction of vancomycin with the membrane models at the air-water interface is modulated by the lipid composition and depends on the intermolecular interactions with the polar group of the molecules that form the monolayer.