Estudo da atividade superficial de lactonas alquiladas e sua interação em modelos de membrana celular
Data
2021-12-13
Autores
Rosa, Matheus Elias 
Orientadores
Caseli, Luciano
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
As lactonas têm apresentado citotoxicidade, com atividade antiprotozoária e antileishmania. Porém, seu mecanismo de ação a nível molecular ainda é desconhecido. Neste trabalho, estudou-se a atividade superficial desse uma lactona alquilada (Isolinderanolide E) frente sua incorporação em modelos de membrana celulares, a partir das monocamadas de Langmuir compostas por lipídios de diferentes naturezas: dipalmitoilfosfatidilcolina (DPPC), dioleilfosfatidilcolina (DOPC), e dipalmitoilfosfatidiletanolamina (DPPE). Um filme contendo apenas a droga. na interface ar-água também foi produzido e avaliado. A lactona, isolada da planta Nectranda oppositifolia, foi solubilizada em clorofórmio e incorporada a filmes monomoleculares, dispersos na interface ar-água. As monocamadas mistas (lactona + lipídio) formadas foram investigadas por isotermas de pressão superficial -área, reologia dilatacional, microscopia no ângulo de Brewster (BAM) e espectroscopia de reflexão-absorção no infravermelho com modulação da polarização (PM-IRRAS), a fim de obter informações sobre a interação droga-membrana. A lactona apresentou tendência a condensar as monocamadas, com exceção da de colesterol. Além disso, a droga tornou os filmes mais fluidos, aumentando sua compressibilidade. Os dados de PM-IRRAS comprovaram a interação da lactona nas partes alquílica e polar dos lipídios, com aumento na desordem causado pelo aumento da relação de confôrmeros gauche/all-trans. Não foi notado rompimento das monocamadas, o que pode estar associado a toxicidade da lactona nestes modelos.
Lactones has been showing cytotoxicity, with antiprotozoal and antileishmanial activity. However, its mechanism of action at a molecular level is still unknown. In this project, the surface activity of an alkylated lactone (Isolinderanolide E) in face of their incorporation in cell membrane models has been studied by Langmuir monolayers composed of lipids from different natures: dipalmitoylphosphatidylcholine (DPPC), dioleylphosphatidylcholine (DOPC), cholesterol and dipalmitoylphosphatidyletanolamine (DPPE). A film formed only by the lactone Isolinderanolide E. was also produced at the air-water interface and characterized. The lactone, isolated from Nectranda oppositifolia, was solubilized in chloroform and incorporated into monomolecular films, spread on the air-water interface. The mixed monolayers (lactone + lipid) formed were characterized with surface pressure-area isotherms, dilatational rheology, Brewster angle microscopy (BAM), and polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS) in order to obtain information about drug-membrane interactions. The lactone showed a tendency to condensate the monolayers, except for the cholesterol ones. Furthermore, the drug made the films more fluid, by increasing their compressibility. PM-IRRA spectra showed interaction by the lactone with polar and alkylic parts of the lipids, in addition to an increase in disorder, associated to the increase of gauche/all-trans conformer ratio. Monolayer rupture was not noted, which might be associated to lactone toxicity in the models studied.
Lactones has been showing cytotoxicity, with antiprotozoal and antileishmanial activity. However, its mechanism of action at a molecular level is still unknown. In this project, the surface activity of an alkylated lactone (Isolinderanolide E) in face of their incorporation in cell membrane models has been studied by Langmuir monolayers composed of lipids from different natures: dipalmitoylphosphatidylcholine (DPPC), dioleylphosphatidylcholine (DOPC), cholesterol and dipalmitoylphosphatidyletanolamine (DPPE). A film formed only by the lactone Isolinderanolide E. was also produced at the air-water interface and characterized. The lactone, isolated from Nectranda oppositifolia, was solubilized in chloroform and incorporated into monomolecular films, spread on the air-water interface. The mixed monolayers (lactone + lipid) formed were characterized with surface pressure-area isotherms, dilatational rheology, Brewster angle microscopy (BAM), and polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS) in order to obtain information about drug-membrane interactions. The lactone showed a tendency to condensate the monolayers, except for the cholesterol ones. Furthermore, the drug made the films more fluid, by increasing their compressibility. PM-IRRA spectra showed interaction by the lactone with polar and alkylic parts of the lipids, in addition to an increase in disorder, associated to the increase of gauche/all-trans conformer ratio. Monolayer rupture was not noted, which might be associated to lactone toxicity in the models studied.
Descrição
Citação
Rosa, Matheus. Estudo da atividade superficial de lactonas alquiladas e sua interação em modelos de membrana celular. Trabalho de Conclusão de Curso - Graduação em Química. Universidade Federal de São Paulo, Diadema. 2021