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

• Grant number: 20/01183-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2020
• End date: March 31, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Luciano Caseli
• Grantee: André Campos Machado
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 14/50869-6 - INCT 2014: on Organic Electronics, AP.TEM

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO, ANDRE CAMPOS; DA SILVA, TAMIRIS REISSA CIPRIANO; RAMINELLI, CRISTIANO; CASELI, LUCIANO. The composition of fusogenic lipid mixtures at the air-water modulates the physicochemical properties changes upon interaction with lysicamine. Biophysical Chemistry, v. 293, p. 8-pg., 2022-12-23. (20/01183-5, 20/12530-8, 18/22214-6, 22/03736-7)

MACHADO, ANDRE CAMPOS; DA SILVA, TAMIRIS REISSA CIPRIANO; RAMINELLI, CRISTIANO; CASELI, LUCIANO. Unsaturation pattern of phosphatidylglycerols modulating the interaction of lysicamine with cells membrane models at the air-water interface. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 222, p. 10-pg., 2023-02-01. (18/22214-6, 19/03239-0, 20/01183-5, 20/12530-8)