New ruthenium complexes with bioactive ligands: investigation of the mechanismo of action

• Grant number: 14/19632-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2015
• End date: February 07, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Angelica Ellen Graminha
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 15/23889-9 - Evaluation of antimetastatic potential of ruthenium complexes, BE.EP.PD

Abstract

For years 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 discover of new drugs to treat cancer are growing and the aim is to find for more effective compounds that have minor side effects and therapeutic resistance. In this sense, compounds containing transition metals have been proposed as antitumor, in particular ruthenium complexes, which present antimetastatic behavior. Several studies have shown that these compounds have lower systemic toxicity compared with the main metalodrugs available for cancer treatment. Therefore, this project aims to study ruthenium complexes containing in its coordination sphere of bioactive natural products such as gallic acid, caffeic acid and p-coumaric acid. Preliminary studies have shown that these complexes ([Ru (OO) (bipy) (dppb)] PF6, where bipy = 2,2'bipiridina, dppb = 1,4-bis (difenfenilfosfine) butane and OO = bioactive ligand) show greater cytotoxicity against human breast carcinoma cell line MDA-MB-231 compared to MCF-7 line. Furthermore, these compounds exhibit low cytotoxicity on non-tumor mouse cell line (L929). Moreover, this project aims to study the possible mechanisms of cell death through the techniques of nuclear fragmentation, topoisomerase inhibition, reactive oxygen species formation, apoptosis assays, zymography and western blotting. However, 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 compounds tested. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GRAMINHA, ANGELICA E.; POPOLIN, CECILIA; DE ARAUJO-NETO, JOAO HONORATO; CORREA, RODRIGO S.; DE OLIVEIRA, KATIA M.; GODOY, LUANI R.; VEGAS, LEGNA COLINA; ELLENA, JAVIER; BATISTA, ALZIR A.; COMINETTI, MARCIA R.. New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 243, p. 14-pg., 2022-12-05. (17/15850-0, 14/19632-0, 21/04876-4, 20/14561-8)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; DULCEY, LIANY LUNA; GODOY, LUANI REZENDE; BARBOSA, MARILIA F.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C.; BATISTA, ALZIR A.. Evaluation of the biological potential of ruthenium(II) complexes with cinnamic acid. Journal of Inorganic Biochemistry, v. 206, MAY 2020. (14/19632-0, 15/24940-8, 16/16312-0)

GRAMINHA, ANGELICA E.; HONORATO, JOAO; CORREA, RODRIGO S.; COMINETTI, MARCIA R.; MENEZES, ANTONIO C. S.; BATISTA, ALZIR A.. A novel ruthenium(II) gallic acid complex disrupts the actin cytoskeleton and inhibits migration, invasion and adhesion of triple negative breast tumor cells. DALTON TRANSACTIONS, v. 50, n. 1, p. 323-335, JAN 7 2021. (14/19632-0, 16/16312-0, 15/24940-8, 13/07600-3)