Antitumor activity and mutagenic potential of New Ruthenium Complexes

• Grant number: 14/25121-8
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2015
• Effective date (End): October 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Amanda Blanque Becceneri
• Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 17/20055-5 - Effects of ruthenium complex trans[Ru(ThySMet)(PPh3)2(bipy)]PF6 on breast tumor cells in three-dimensional culture, BE.EP.DR

Abstract

Cancer is among the leading causes of death in the world. Cancer treatment requires a careful selection of one or more methods of intervention. The majority of drugs currently used in chemotherapy causes DNA damage, in tumor cells and also normal cells, therefore the development of new chemotherapeutic agents is challenging, since these chemotherapeutic agents should be able to act selectively to kill or inhibit the growth only of tumor cells. The medicinal inorganic chemistry is a growing area, initially fueled by the discovery of cisplatin about 40 years ago. Cisplatin and successive generations of platinum-based antitumor drugs has shown that the metal complexes may play an important role in cancer treatment. These complexes have remarkable features that can be exploited for the development of new drugs. The octahedral ruthenium complexes have attracted great attention and highlighted interest, since they have characteristics that make them suitable for medical application. The activity of metal ions can be improved by connecting with biologically active compounds. The linker N, N'-dialkyl-N-aciltioureas is very versatile, and small changes in their structure can easily be carried out and lead to different physical and chemical properties. The design of antitumor drugs is one of the most promising strategies for increasing their cytotoxicity and minimize toxicity. Given the above, the objective of the project is to select among different molecules, a new and powerful ruthenium complex, which may be a candidate for antitumor drug through in vitro and in vivo trials.

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)

BECCENERI, AMANDA B.; FUZER, ANGELINA M.; PLUTIN, ANA M.; BATISTA, ALZIR A.; LELIEVRE, SOPHIE A.; COMINETTI, MARCIA R. Three-dimensional cell culture models for metallodrug testing: induction of apoptosis and phenotypic reversion of breast cancer cells by the trans-[Ru(PPh3)(2)(N,N-dimethyl-N-thiophenyl-thioureato-k(2)O,S)(bipy) ]PF6 complex. INORGANIC CHEMISTRY FRONTIERS, v. 7, n. 16, p. 2909-2919, AUG 21 2020. Web of Science Citations: 0.

BECCENERI, AMANDA BLANQUE; FUZER, ANGELINA MARIA; POPOLIN, CECILIA PATRICIA; CAZAL, CRISTIANE DE MELO; DOMINGUES, VANESSA DE CASSIA; FERNANDES, JOAO BATISTA; VIEIRA, PAULO CEZAR; COMINETTI, MARCIA REGINA. Acetylation of cedrelone increases its cytotoxic activity and reverts the malignant phenotype of breast cancer cells in 3D culture. Chemico-Biological Interactions, v. 316, JAN 25 2020. Web of Science Citations: 0.

BECCENERI, AMANDA BLANQUE; POPOLIN, CECILIA PATRICIA; MARIA PLUTIN, ANA; MAISTRO, EDSON LUIS; CASTELLANO, EDUARDO ERNESTO; BATISTA, ALZIR AZEVEDO; COMINETTI, MARCIA REGINA. The trans-[Ru(PPh3)(2)(N,N-dimethyl-N `-thiophenylthioureato-k(2)O,S)(bipy)] PF6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo. Journal of Inorganic Biochemistry, v. 186, p. 70-84, SEP 2018. Web of Science Citations: 2.