Evaluation of antimetastatic potential of ruthenium complexes

• Grant number: 15/23889-9
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): February 05, 2016
• Effective date (End): January 04, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Angelica Ellen Graminha
• Supervisor abroad: Nicholas Patrick Farrell
• Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Local de pesquisa : Virginia Commonwealth University (VCU), United States
• Associated to the scholarship: 14/19632-0 - New ruthenium complexes with bioactive ligands: investigation of the mechanismo of action, BP.PD

Abstract

Cancer is the second cause of death worldwide, being preceded only by cardiovascular diseases. Global estimates indicate that cancer will increasingly gain more importance in the morbidity and mortality in the coming decades if no preventive action is taken. Research groups focusing on the discovery of new drugs to treat cancer are growing and the aim is to find more effective compounds having fewer side effects and therapeutic resistance. In this sense, compounds containing transition metals have been proposed as antitumor; in particular ruthenium complexes have shown a new perspective for cancer treatment. Some of them exhibit antitumor activity superior to cisplatin, as well as lower toxicity. Therefore, this project aims to study Ru(II) complexes containing bioactive natural products such as gallic, caffeic or p-coumaric acids in its coordination sphere. Preliminary studies have shown that these complexes ([Ru(OO)(bipy)(dppb)]PF6, where bipy = 2,2'-bipiridine, dppb = 1,4-bis(diphenylphosphine)butane and OO = bioactive ligand) show greater cytotoxicity against human breast carcinoma cell line MDA-MB-231, compared to MCF-10A non-tumor cell line, and were able to inhibit migration and invasion of MDA-MB-231 cells at low concentrations. Complex containing p-coumaric ligand inhibits the adhesion of MDA-MB-231 cells to different extracellular matrix proteins. Moreover, this project aims to study the possible mechanisms of cell death through the investigation of the complexes interaction with proteoglycans and topoisomerase I. It is expected that by means of chemical and biological data, it will be possible to elucidate a mechanism of action, as well as a correlation between structure and activity of the complexes tested.