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

Author(s)

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

• Document type: Journal article
• Source: Applied Surface Science; v. 426, p. 10-pg., 2017-12-31.

Abstract

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. (AU)

• FAPESP's process: 15/23446-0 - Smart surfaces: nanostructured and bioinspired systems for the investigation of molecular interactions in membrane models and for the production of devices for biosensors and environmental analysis
• Grantee: Luciano Caseli
• Support Opportunities: Regular Research Grants