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Ruthenium nitrosil complex as producer of nitric oxide and singlet oxygen: FOTOBIOLOGICAL studies, BICHEMICAL and their potential therapeutical aplication

Grant number: 14/03964-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Andréia Machado Leopoldino
Grantee:Fernando Postalli Rodrigues
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):14/25071-0 - Assessment of metallocompounds using synchrotron FTIR spectromicroscopy and measurements on living cells, BE.EP.PD

Abstract

Elements supporting this project: (i) nitric oxide (NO) is a biological messenger of physiological and anticancer processes, (ii) its functions depend on its concentration and site of action, (iii) the use of NO donos compounds in clinical treatments such as photodynamic therapy (PDT) reach systems capable of releasing NO in a controlled way on biological systems, (iv) ruthenium- nitrosyl complex may be thermodynamically stable, but photochemically active, (v) the NO associated the release of singlet oxygen (1O2), increases the production of reactive oxygen species (ROS) and nitrogen (ERONs), (vi) both reactive species are involved in the modulation of cell death , eg apoptosis, (vii) species produce both NO and 1O2 photodynamic therapy against câncer.This project proposes the study of compounds that absorb radiation in the region of therapeutic window and which provide photoinduced electron transfer, in the presence of nitrosyl ruthenium complexes, can produce NO. Based on this the goal of this project is the study of energy transfer between Quantum Dots and [ (cp -R ) Runo (NO2) ] complex trans - ( PC -R is modified phthalocyanine ) and the type [ RuN4L (NO)]n+ and or [ RuN4L (NO2) ](1 -n +) (where N is nitrogen ligands and L can be pyridine , 4 - picoline and 4 - acetylpyridine), producing agents of reactive oxygen species ( ROS ) and nitrogen ( ERONs ) by light irradiation in the region of 500 nm to 700 nm which induce cell death in tumors.It will assess biochemical mechanisms related to interaction ruthenium complex as well as cell identification studies, activation and regulation of the signaling pathways of cell death. To this end, the following analysis tools will be used: proteomics, western blotting, confocal microscopy, flow cytometry as well as gene manipulation techniques, i.e., silencing / deletion of genes of interest. (AU)

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