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Effects of ruthenium compounds on the topoisomerase i enzyme as antitumoral mechanism

Grant number: 13/20078-4
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 06, 2014
Effective date (End): October 05, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Alzir Azevedo Batista
Grantee:Mariana Santoro de Camargo
Supervisor abroad: Alessandro Desideri
Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Local de pesquisa : Università degli Studi di Roma Tor Vergata, Italy  
Associated to the scholarship:12/21529-7 - "evaluation of antitumoral activity of ruthenium compounds: study of mutagenicity, cytotoxicity, topoisomerases inhibition and alterations on genic expression", BP.PD


Cancer is predicted to be an increasingly important cause of morbidity and mortality in the next few decades. Because of therapeutic resistance and side effects, a wide range of studies are focused on the discovery of new drugs for cancer treatment. In view of this, transition metal-based compounds have been proposed as potential antitumor activity and antimestastatic behavior, in particular complexes based on ruthenium. Different studies show that these compounds presents lower systemic toxicity than the major metallodrugs available to cancer treatment. Recently, different ruthenium complexes have received considerable attention as topoisomerase inhibitors due to their rich photochemical properties and varied coordination forms. Topoisomerases are involved in many vital cellular processes that influence DNA replication, transcription, recombination, integration, and chromosomal segregation. Many studies have shown that topoisomerases are important therapeutic targets in cancer chemotherapy. Preliminary studies reported high cytotoxicity of ruthenium compounds with formula [Ru(N-S)(bipy)(dppb)]PF6, where bipy = 2,2'-bipyridine and dppb = 1,4-bis(difenfenilfosfina) butane and N-S = pySH (2-mercaptopiridina), HSpym (2-mercaptopirimidina) and SpymMe2 (4,6-dimetil-2-mercaptopirimidina), against human hepatocellular liver carcinoma (HepG2), where the IC50 value were lower than doxorubicin and the mutagenicity were negative when assessed by Ames Test. Thus, the aim of this study is to evaluate the capacity of these compounds on inhibit the topoisomerase I activity, in view of elucidate the possible mechanisms of action contributing to the development of a new antitumor drug. (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)
DE GRANDIS, RONE A.; DE CAMARGO, MARIANA S.; DA SILVA, MONIZE M.; LOPES, ERICA O.; PADILHA, ELIAS C.; RESENDE, FLAVIA A.; PECCININI, ROSANGELA G.; PAVAN, FERNANDO R.; DESIDERI, ALESSANDRO; BATISTA, ALZIR A.; VARANDA, ELIANA A. Human topoisomerase inhibition and DNA/BSA binding of Ru(II)-SCAR complexes as potential anticancer candidates for oral application. BIOMETALS, v. 30, n. 3, p. 321-334, JUN 2017. Web of Science Citations: 8.
DE CAMARGO, MARIANA S.; DA SILVA, MONIZE M.; CORREA, RODRIGO S.; VIEIRA, SARA D.; CASTELLI, SILVIA; D'ANESSA, ILDA; DE GRANDIS, RONE; VARANDA, ELIANA; DEFLON, VICTOR M.; DESIDERI, ALESSANDRO; BATISTA, ALZIR A. Inhibition of human DNA topoisomerase IB by nonmutagenic ruthenium( II)-based compounds with antitumoral activity. METALLOMICS, v. 8, n. 2, p. 179-192, 2016. Web of Science Citations: 20.

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