Chemical reactivity of nitrosyl ruthenium compounds. Chemical, kinetical and biological studies

• Grant number: 12/02968-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2012
• End date: May 31, 2014
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Santana da Silva
• Grantee: Joicy Santamalvina dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Nitric oxide (NO) is a radical species involved in many biological processes. Despite the great importance of the NO in the biological system, studies on their pharmacological properties and physiological is limited due to their high reactivity and short half-life. Thus, the development of compounds that can release NO, may be an alternative to these problems and potentially be used as therapeutic agents. One of these possibilities is the action of NO as anticancer agent. Based on that this project aims to synthesize general species that can act as NO donor agents by reduction process and evaluate the site of NO release through the use of luminescent compounds. The specificity of these compounds will be achieved through interaction sugar-{Ru-NO species} obtained when cis-[Ru (bpy-sugar)2(py-R)(NO)]3+ (I) is exposed to metastatic cells. In these studies are summarized species [Ru(bpy-sugar)2(py-R)NO](PF6)3 wherein R =fluorophore ligand (BODPY), [Ru(bpy)2(py-R)NO]3+ (bpy = 2,2 '-bipyridine) and [Ru(L)4(py-R)NO]+3 (py=pyridine, 4-picoline and 4-acetylpyridine). The chemical characterization and kinetics of these systems will be evaluated by electrochemical and spectrophotometric techniques. The kinetics of release of nitric oxide from the reduction of [Ru(bpy-sugar)2(py-R)NO]+3 will be evaluated using a nitric oxide sensor and spectroscopic methods. Cytotoxicity is determined by the MTT assay and flow cytometry. Comparison of the cytotoxic effect of (I) species [Ru(bpy)2 (py-R)NO]+3 will evaluate the "uptake" of the compound according to structural changes in the bipyridine ligand. The mitochondrial membrane potential will be estimated using rhodamine 123.