Loyanne C B Ramos1, Fernando P Rodrigues1, Juliana C Biazzotto1, Sergio de Paula Machado2, Leonardo D Slep3, Michael R Hamblin4,5, Roberto S da Silva6,7,8. 1. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 2. Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-590, Brazil. 3. Departamento de Química Inorgánica, Analítica y Química Física and INQUIMAE, CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA, Buenos Aires, Argentina. 4. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA. 5. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. 6. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. silva@usp.br. 7. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA. silva@usp.br. 8. Department of Dermatology, Harvard Medical School, Boston, MA, 02115, USA. silva@usp.br.
Abstract
The rational design of anti-cancer agents includes a new approach based on ruthenium complexes that can act as nitric oxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based on bis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity properties against the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2- conjugated to a polyclonal antibody IgG (anti-VDAC) recognizing a cell surface marker. UV-visible bands of the ruthenium complex were assigned with the aid of density functional theory, which also allowed estimation of the structures that explain the biological effects of the ruthenium complex-IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3- with mitochondria was evaluated due to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody. The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3--anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3- complex. We suggest that this effect is due to site-specific interaction of the complex followed by NO release.
The rational design of anti-n class="Disease">cancer agents includes a new approach based on ruthenium complexes that can act as nitric oxide (NO) donor agents against specific cellular targets. One of the most studied classes of those compounds is based on bis(bipyridine) ruthenium fragment and its derivative species. In this work, we present the chemical and cytotoxicity properties against the liver hepatocellular carcinoma cell line HepG2 of cis-[RuII(NO+)Cl(dcbpy)2]2- conjugated to a polyclonal antibody IgG (anti-VDAC) recognizing a cell surface marker. UV-visible bands of the ruthenium complex were assigned with the aid of density functional theory, which also allowed estimation of the structures that explain the biological effects of the ruthenium complex-IgG conjugate. The interaction of cis-[RuII(NO+)Cl(dcbpy)2]3- with mitochondria was evaluated due to the potential of these organelles as anti-cancer targets, and considering they interact with the anti-VDAC antibody. The cytotoxicity of cis-[RuII(NO+)Cl(dcbpy)2]3--anti-VDAC antibody was up to 80% greater in comparison to the free cis-[RuII(NO+)Cl(dcbpy)2]3- complex. We suggest that this effect is due to site-specific interaction of the complex followed by NO release.
Authors: José Carlos Toledo; Luiz Gonzaga de França Lopes; Armindo Antonio Alves; Lucia Pereira da Silva; Douglas Wagner Franco Journal: J Inorg Biochem Date: 2002-04-28 Impact factor: 4.155