Correlation of [RuCl3(dppb)(VPy)] Cytotoxicity with its Effects on the Cell Membranes: An Investigation Using Langmuir Monolayers as Membrane Models

Correlation of [RuCl3(dppb)(VPy)] Cytotoxicity with its Effects on the Cell Membranes: An Investigation Using Langmuir Monolayers as Membrane Models

Author Sandrino, B. Google Scholar
Tominaga, T. T. Google Scholar
Nobre, T. M. Google Scholar
Scorsin, L. Google Scholar
Wrobel, E. C. Google Scholar
Fiorin, B. C. Google Scholar
Araujo, M. P. de Google Scholar
Caseli, L. Autor UNIFESP Google Scholar
Oliveira, O. N. Google Scholar
Wohnrath, K. Google Scholar
Institution Univ Estadual Ponta Grossa
Univ Estadual Centro Oeste
Universidade de São Paulo (USP)
Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Abstract One of the major challenges in drug design is to identify compounds with potential toxicity toward target cells, preferably with molecular-level understanding of their mode of action. in this study, the antitumor property of a ruthenium complex, mer-[RuCl3(dppb)(VPy)] (dppb =1,4-bis(diphenylphosphine)butane and VPy = 4-vinylpyridine) (RuVPy), was analyzed. Results showed that this compound led to a mortality rate of 50% of HEp-2 cell with 120 +/- 10 mu mol L-1, indicating its high toxicity. Then, to prove if its mode of action is associated with its interaction with cell membranes, Langmuir monolayers were used as a membrane model. RuVPy had a strong effect on the surface pressure isotherms, especially on the elastic properties of both the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) phospholipids. These data were confirmed by polarization-modulated infrared reflectionabsorption spectroscopy (PM-IRRAS). in addition, interactions between the positive group from RuVPy and the phosphate group from the phospholipids were corroborated by density functional theory (DFT) calculations, allowing the determination of the Ru complex orientation at the airwater interface. Although possible contributions from receptors or other cell components cannot be discarded, the results reported here represent evidence for significant effects on the cell membranes which are probably associated with the high toxicity of RuVPy.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
nBioNet (Brazil)
Date 2014-09-11
Published in Journal of Physical Chemistry B. Washington: Amer Chemical Soc, v. 118, n. 36, p. 10653-10661, 2014.
ISSN 1520-6106 (Sherpa/Romeo, impact factor)
Publisher Amer Chemical Soc
Extent 10653-10661
Access rights Closed access
Type Article
Web of Science ID WOS:000341619600011

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