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Grant number: 12/21529-7
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2013
Effective date (End): November 07, 2016
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal Investigator:Alzir Azevedo Batista
Grantee:Mariana Santoro de Camargo
Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Associated scholarship(s):13/20078-4 - Effects of ruthenium compounds on the topoisomerase i enzyme as antitumoral mechanism, BE.EP.PD


Currently, a wide range of studies are focused on the discovery of drugs for cancer treatment, because the majority of available anticancer drugs presents no selectivity to cancer cells, causing various side effects. Metal complexes remain an important resource for the generation of anticancer drugs development, such as cisplatin that represents one of the most active and clinically useful agents used in the treatment of cancer, achieving cures in a lot of cancer types but induces high toxicity to the kidney and development of acquired resistance. In view of this, transition metal-based compounds have been proposed as potential antitumor activity and antimestastatic behavior, in particularcomplexes based on ruthenium. Different studies show that these compounds presents lower systemictoxicity than the major metallodugs available to cancer treatment. Thus, researches on the mechanism of action become important to define the real clinical potential of these complexes, contributing to the development of a new antitumor drug. Preliminary studies reported high cytotoxicity of ruthenium compounds with formula [Ru(Lap)(PPh3)2(Me-bipy)]PF6, [Ru(Lap)(PPh3)2(MeO-bipy)]PF6,[Ru(Lap)(Me-bipy)(dppb)]PF6 e [Ru(Lap)(MeO-bipy)(dppb)]PF6 [Me-bipy = 4,4´-dimetyl-2,2'-bipyridine, MeO-bipy = 4,4´-dimetoxy-2,2´-bipyridine; Lap = lapachol e dppb = 1,4-bis(difenfenilfosfino)butane], against cancer cell line MDA-MB-231 (breast cancer) and lowercitotoxicity on non-tumoral cells. Therefore, in order to characterize the biological activity of these compounds, the aim of this study is to determine the mutagenic activity by Ames test, with and without metabolism and inhibition of topoisomerases I and II. Evaluate, using human hepatocellular liver carcinoma cell line (HepG2), the cytotoxicity and influence on DNA damage (Citoma test) induced by these compounds. Moreover, the capacity in alter gene expression of cancer cells by PCR Array will be studied in order to contribute to their recommendation as a therapeutic agent.

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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 CAMARGO, MARIANA S.; DE GRANDIS, RONE A.; DA SILVA, MONIZE M.; DA SILVA, PATRICIA B.; SANTONI, MARIANA M.; EISMANN, CARLOS E.; MENEGARIO, AMAURI A.; COMINETTI, MARCIA R.; ZANELLI, CLESLEI F.; PAVAN, FERNANDO R.; et al. Determination of in vitro absorption in Caco-2 monolayers of anticancer Ru(II)-based complexes acting as dual human topoisomerase and PARP inhibitors. BIOMETALS, v. 32, n. 1, p. 89-100, . (12/21529-7, 16/22429-7, 16/16312-0)
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; et al. Inhibition of human DNA topoisomerase IB by nonmutagenic ruthenium( II)-based compounds with antitumoral activity. METALLOMICS, v. 8, n. 2, p. 179-192, . (14/10516-7, 12/21529-7, 13/20078-4)

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