ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P36. Diruthenium(II,III)-ibuprofen Metallodrug: Interaction with Human
Serum Albumin and Effects on Leukemic Tumor Cells
D. de Oliveira Silva, R.R.P. Santos
a Departamento de Quimica Fundamental, Instituto de Quimica da Universidade de São Paulo, Av. Prof. Lineu
Prestes, 748, B2T, 05508-000, São Paulo, SP, Brazil
e-mail: deosilva@iq.usp.br
Ruthenium compounds are of current interest for anticancer chemotherapy. Chemical and biological properties
of Ru-NSAIDs (nonsteroidal anti-inflammatory drugs) have been studied in our laboratory. Recently,
a diRu(II,III)-ibuprofen (Ruibp) complex was found to inhibit proliferation of C6 rat glioma cells with induction
of cell death [1,2]. Interestingly, it also acts as anti-inflammatory with reduced gastrointestinal ulceration [3].
Here, the interaction with human serum albumin (HSA) and a novel biological property for Ruibp are reported.
HSA conformational change was detected by UV circular dichroism and percentages of secondary structure were
calculated for various HSA:Ruibp molar ratios. Fluorescence quenching of HSA induced by Ruibp in
physiological condition was observed by monitoring (excitation, 295 nm) the emission of tryptophan, indicating
that the conformation of the hydrophobic pocket in sub domain IIA is affected. The electronic spectrum of Ruibp
in solution of histidine suggests that Ru can bind to HSA by imidazole N of this amino acid. SDS-PAGE
electrophoresis shows no cleavage of HSA in the presence of complex. Preliminary MTT assays show that
Ruibp exhibits cytotoxic effect on K562 human myeloid leukemic cells at relatively low concentrations
(60 µmol/L). It is an interesting result since NSAIDs can induce apoptosis and inhibit proliferation of leukemic
cells at higher concentrations (indomethacin: IC50= 310 µmol/L [4]).
Acknowledgment: FAPESP, CNPq.
References:
[1] G. Ribeiro, M. Benadiba, A. Colquhoun, D. de Oliveira Silva, Polyhedron, 27, 1131 (2008).
[2] M. Benadiba, G. Ribeiro, D. de Oliveira Silva, A. Colquhoun. Neuron Glia Biology S1- Glia Cells in Health
and Disease 3, S127, B148 (2007)
[3] A. Andrade, S.F. Namora, R.G. Woisky, G. Wiezel, R. Najjar, J.A.A. Sertie, D. de Oliveira Silva. J. Inorg.
Biochem., 81, 23 (2000).
[4] G.S. Zhang, C.Q. Tu, G.Y. Zhang, G.B. Zhou, W.L. Zheng, Leukemia Research, 24, 385 (2000).
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