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Investigation of the effectiveness of ruthenium complexes in the treatment of cancer: in vitro and in vivo studies

Grant number: 21/14210-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2022
Effective date (End): August 19, 2022
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Cooperation agreement: CNPq - Pronex
Principal researcher:Eduardo Ernesto Castellano
Grantee:Katia Mara de Oliveira
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:17/15850-0 - X-ray diffraction as a tool in potential drug development, AP.TEM

Abstract

The development of metallic compounds to find new drug candidates for the treatment of cancer has gained increasing importance in the scientific field, considering that cancer is a serious public health problem worldwide. Therefore, several metallic compounds have been studied, seeking to identify more selective and effective compounds. In particular, ruthenium-based compounds have shown promising anticancer properties, which has encouraged many research groups to develop studies focused on this metal. In this context, the aim of the present project is to investigate the antitumor potential of new ruthenium complexes, through in vitro and in vivo assays, being an integral part of the thematic project "X-Ray Diffraction as a Tool in the Development of Potential Drugs" (2017 /15850-0). The possible mechanism of action of ruthenium complexes containing 5ý-diketones (O,O), mercaptopyridines and mercaptopyrimidines (N,S) as ligands, with general formulas [Ru(56-p-cimene)(N,S)(P)]PF6 and [Ru(O,O)(P)2(N,N)]PF6, where P refers to monophosphines and N,N to 2,2'-bipyridine ligands, will be investigated. In vitro and in vivo tests will be performed, such as analysis of the mechanism of cell death by apoptosis, cell cycle, mitochondrial depolarization, and formation of reactive oxygen species. The most promising compounds will be selected for in vivo assays, which will analyze the antitumor efficiency in melanoma induced in C57BL/6 mice, as well as toxicological parameters of these treatments in kidney, liver, and bone marrow. Finally, the aim is to correlate chemical and biological data seeking to make a relationship between the structure and activity of the studied complexes. (AU)

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