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    Interaction of 3 ',4 ',6 '-trimyristoyl-uridine derivative as potential anticancer drug with phospholipids of tumorigenic and non-tumorigenic cells

    Year: 2017

    Journal: Appl. Surf. Sci., Volume 426, DEC 31, page 77–86

    Authors: Grosso Salis, Luiz Fernando; Jaroque, Guilherme Nunez; Berrio Escobar, Jhon Fernando; Giordani, Cristiano; Martinez Martinez, Alejandro; Marquez Fernandez, Diana Margarita; Castelli, Francesco; Sarpietro, Maria Grazia; Caseli, Luciano

    Organizations: University of Antioquia [CODI CIQF-155 2012-2014]; Brazilian agency "Conselho Nacional de Desenvolvimento Cientifico e Tecnologico" (CNPq); Brazilian agency "Fundacao de Amparo a Pesquisa do Estado de Sao Paulo", FAPESP [2015/23446-0]

    Keywords: Anticancer drugs; Uridine derivative; Langmuir monolayers; Air-water interface

    Investigating the mechanism of action of drugs whose pharmaceutical activity is associated with cell membranes is fundamental to comprehending the biochemical and biophysical processes that occur on membrane surfaces. In this work, we investigated the interaction of an ester-type derivative of uridine, 3',4',6'-trimyristoyl uridine, with models for cell membranes formed by lipid monolayers at the air-water interface. For that, selected lipids have been chosen in order to mimic tumorigenic and non-tumorigenic cells. For mixed monolayers with 2-dipalmitoyl-sn-g/ycero-3-phosphocholine (DPPC) or l,2-dihexadecanoyl-sn-g/ycero-3-phospho-L-serine (DPPS), the surface pressure-area isotherms exhibited a noticeable shift to lower areas in relation to the areas predicted for ideal mixtures, indicating a condensation of the monolayer structure. Changes in the viscoelastic properties of the interfacial film could be inferred by analyzing the compressibility modulus of the monolayer. Structural and morpho-logical changes were also evidenced by using vibrational spectroscopy and Brewster angle microscopy, respectively, with distinctive effects on DPPC and DPPS. As conclusion we can state that the lipid compo sition of the monolayer modulates the interaction with this lipophilic drug, which may have important implications in understanding how this drug acts on specific sites of the cellular membrane. (C) 2017 Elsevier B.V. All rights reserved.
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