Ruthenium complexes as nitric oxide deliver agents. determination of the reactive species formed and their cytotoxic effects

• Grant number: 11/21882-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: December 01, 2011
• End date: April 30, 2012
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Roberto Santana da Silva
• Grantee: Tassiele Andréa Heinrich
• Supervisor: Jon M. Fukuto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Sonoma State University (SSU), United States
• Associated to the scholarship: 08/09935-4 - Biological activity of ruthenium complexes as Nitric oxide donor agents in neoplasic cell lines. Chemical, photochemical and citotoxic aspects, BP.DR

Abstract

Nitric oxide (NO) is a biological messenger that has vital importance in many physiological processes, such as cardiovascular control, the neural signaling and defense against microorganisms and tumors. However, the formation of other reactive species, resulting from chemical reactions of NO with the actual biological environment, such as the auto-oxidation of NO, imposes limits on the understanding of the possible cellular mechanisms involved in biological responses. Given the potential pharmacological and offers benefits due NO, there is a need for development of compounds that can stabilize the NO until it's released. One possibility involves nitrosyl ruthenium complexes, whose strategy is to use compound that is thermodynamically stable but photochemically active. Based on this we have suggested the use of [{Rupc(pz)2(Ru(bpy)2NO)2}](PF6)6 (pc = phthalocyanine) and [Ru(terpy)(bdq)NO](PF6)3 as NO deliver agent. The [{Rupc(pz)2(Ru(bpy)2NO)2}] (pc = phthalocyanine) is also singlet oxygen (1O2) producer and will give us the opportunity to understand the effect of NO and 1O2 as citotoxyc agent.The photoinduced cytotoxical properties of [{Rupc(pz)2(Ru(bpy)2NO)2}] (pc = phthalocyanine) will be described in this project. Its biological effect will be studied in the presence and absence of therapeutic window light irradiation (600 - 850 nm) in cancer cell line by means nitric oxide and singlet oxygen production. The effect of reactive oxygen and nitrogen species will be described and citotoxycal mechanism caused by the nitrosyl ruthenium complexes will be evaluated. Furthermore, the nitric oxide release followed by singlet oxygen production upon light irradiation of the nitrosyl ruthenium complex should produce two radicals capable to improve photodynamic therapy, a clinical therapy which efficiency is actually limited and dependent on oxygen concentration. The knowledge of the citotoxycity mechanism performed with [{Rupc(pz)2(Ru(bpy)2NO)2}]6+ and [Ru(terpy)(bdq)NO]3+ is crucial to understand the synergistic effect of NO and 1O2. (AU)