Ruthenium phthalocyanine complexes as prototypes for metallo-drugs photochemically active: photobiological studies, theranostic effect and metabolism evaluation

• Grant number: 13/08851-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2014
• End date: January 31, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Santana da Silva
• Grantee: Roberto Santana da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 15/50101-3 - Cytotoxicity and photo-cytotoxicity of nitrosyl ruthenium anticancer drug in aqueous solution or incorporated in a drug delivery system.an innovative purpose for metal based drug, AP.R SPRINT

Abstract

Nitric oxide (NO) is a vital biological messenger that has importance in many physiological processes, such as controlling cardiovascular function, neural signaling and defense against microbes and tumors. In addition, NO is also anticancer agent, which would enable the use of NO donor compounds in clinical treatments, for example in photodynamic therapy (PDT). Based on the chemical and biological characteristics of NO that is vital search systems that can release NO in a controlled way in biological system. One possibility involves nitrosyl ruthenium complexes, whose strategy would be to use compounds that would be thermodynamically stable, but photochemically active. Compounds that absorb in the therapeutic window are amenable to be used in clinical therapy and could propitiate photoinduced electron transfer in the presence of nitrosyl ruthenium complexes, producing NO. Based on that the goal of this project is to synthesize compounds like [Ru(NO)(pc-R)NO2] as well coupled to quantum-dots and study production of reactive oxygen species (ROS) and nitrogen (ERONs) by light irradiation in 500 nm to 700 nm region by photoinduced electron and energy transfer. Measurements of NO, singlet oxygen and its derivatives will be determined for different oxygen concentrations. Cytotoxicity in cancer cell lines will be evaluated. Photochemical studies by light irradiation in the visible region, will be held both in deaerated medium as a function of oxygen concentration. Photophysical and kinetic methods will be conducted in order to describe the process of photoinduced energy transfer, observed in the species under study. Some biochemical processes related to interaction ruthenium complex-cell will be evaluated for ruthenium interaction with cell surface proteoglycans by labeling with fluorophores; phosphorylation of Akt and mitogen-activated protein kinase (MAPK) Assessment of AMPK (AMP-activated protein kinase ), JNK (c-jun terminal kinase-N) and ATF3 (factor 3 transcriptional activation) in response to treatment with the ruthenium complex in the aforementioned cell lines. Later we will evaluate the cytotoxic potential of species which produce both nitric oxide (NO) and singlet oxygen (1O2) in photodynamic therapy of cancers. Parallel studies are also performed photochemical and photophysical quantizing to ROS and ERONs in aqueous medium. (AU)

Filed patent(s) as a result of this research project