A new nitrosyl ruthenium complex: Synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl2NO(BPA)] is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis. (C) 2011 Elsevier Masson SAS. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP (Sao Paulo State Research Foundation)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq (Brazilian National Research Council)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)FAPERJ (Rio de Janeiro State Research Foundation)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)CAPES (Coordination for the Improvement of Higher Education Personnel