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    Estudo da interação do metronidazol em modelos de membrana
    (Universidade Federal de São Paulo, 2018-05-24) Rodrigues, Jefferson Carnevalle [UNIFESP]; Caseli, Luciano [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Interactions of bactericidal and antiprotozoal drugs with cell membranes could be better understood at the molecular level if nanostructured systems are employed. This study aimed to study the action of the drug Metronidazole in Langmuir films of phospholipids, which are used as simple models of cell membranes. The phospholipids used were dipalmitoylphosphatidylcholine (DPPC), dipalmitoylfosfatil serine (DPPS) and dipalmitoylfosfatil glycerol (DPPG), cholesterol (COL), 1,2 Dioleoyl-sn-glycero-3-phosphocoline (DOPC), and combinations of glycoproteins with dipalmitoylphosphatidylcholine (GLICOP +DPPC), peptidoglycan with DPPG (Pep+DPPG) and lipopolysaccharides with DPPG (LPS+DPPG). The lipids were spread on the air-water interface, and the drug injected into the aqueous subphase. The adsorption of the drug was evaluated by surface pressure measurements, infrared spectroscopy and Brewster angle microscopy (BAM). The drug causes pronounced effects on pressure-area isotherms for DPPC, DPPS, DPPG, Cholesterol, Glycoproteins + DPPC, Lipopolysaccharides + DPPG and Peptidoglycans+DPPG condensing the monolayer (shifts the isotherms to smaller areas per molecules at a given pressure), but expanding DPPG and DPPE monolayers. Infrared spectroscopy shows significant changes in the bands related to the stretch of methyl, increasing the molecular order for DPPS, DOPC, DPPE monolayers, and mixtures of DPPC with glycoproteins, whereas for DPPG, DPPG + LPS and DPPG + Pep the molecular order has a decrease, can also be observed probable interactions in the hydrophilic regions of the film when in the presence of mixed monolayers (LPS + DPPG and Pep + DPPG). BAM images show that the surface morphology of the lipid monolayers also changed with the presence of the drug, causing molecular aggregation, but with different morphological configurations for each film. This shows that the interaction of Metronidazole in the monolayer is modulated by the lipid composition at the air-water interface, as well as the drug-lipid interactions. We hope these results have a relevant impact on the understanding of how bioactive compounds act in microbial cells and in the pursuit for proposals of mechanisms at the molecular level.