Interaction of lisycamine with models of cellular membrane at the air-water interface

Abstract

In this project, we intend to study the interaction of lisycamine, an aporphinoid alkaloid found in plants of the family Annonaceae, which has leishmanicidal and antitumor activities, with cell membrane models. From the thermodynamic, electrical, morphological, rheological and spectroscopic characterization of the models, we aimed to understand at the molecular level the interactions of the alkaloid with the cell membrane and to associate with the antitumor action of this compound. We will obtain lisycamine from its total synthesis, which will involve, as a key step, the cycloaddition reaction [4 + 2], followed by hydrogen migration, producing the aporphinoid skeleton, which through four more reaction steps the final compound will be obtained. The evaluation in cell membrane models will be done with the incorporation of the alkaloid in Langmuir films formed by the lipids dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidylcholine (DOPC) and dioleoylphosfatidilserine (DOPS). These lipids will be spread on the the air-water interface forming pure or mixed monolayers. The action of the alkaloid in the monolayers will be evaluated through surface pressure-are isotherms, pressure-time stability isotherm, infrared absorption-reflection spectroscopy (PM-IRRAS), surface potential-area isotherms, determination of viscoelastic parameters by the method of oscillating barriers, and Brewster angle microscopy (BAM). The results will be evaluated from a biological perspective, looking for evidences of the interaction of lisycamine with cell membranes of healthy and tumor cells in order to understand the possible mechanism involving its cytotoxic action. Thus, this project aims to study the physicochemical properties of a biologically relevant molecule and the impact on its physiological actions. Basic knowledge of the behavior of biomolecular systems helps the development of biosensors, bioelectronic devices, drug distribution and control systems and applications in Tissue Engineering. (AU)