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Evaluation of mutagenic activity of Ruthenium (II) heteroleptic complexe with anti- Mycobacterium tuberculosis activity

Grant number: 12/22364-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2013
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Principal Investigator:Flávia Aparecida Resende Nogueira
Grantee:Rone Aparecido de Grandis
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Mycobacterium tuberculosis, the agent of tuberculosis, is responsible for the deaths of millions of people around the world and global economic losses of billions of dollars. Its mortality rate decreased globally in 2007, however, multidrug-resistant strains and co-infection with HIV have hindered attempts to control tuberculosis. Since 1960 no drugs against M. tuberculosis have been developed. New studies show Ruthenium(II) complexes as strong medicine for new therapy against tuberculosis. These complexes have been tested against various bacteria and current studies indicate excellent results with high activity against M.tuberculosis. However, even with promising antimycobacterial effects, it is essential to evaluate the safety of these complexes to human health. In this context, the evaluation of the mutagenic potential of these complexes is critical to ensure its use without showing the risk of developing cancers. Thus, this study aims to evaluate the mutagenic activity of cis-[Ru(pic)(dppe)2]PF6 (CPX1) complexe by means of reverse gene mutation assays with Salmonella typhimurium (Ames test) and cytome. The Ames test will be performed according to the methodology of preincubation in the presence and absence of metabolic activation, TA98, TA97, TA100, and TA102 of S. typhimurium. The cytometry assay will be performed in CHO-K1 and HepG2 culture cells, where the frequency of micronuclei, nucleoplasmic bridges, and nuclear budding will be analyzed as parameters, as well as the nuclear division index. With the results of these assays, it will be possible to elucidate the mechanisms by which this complexe interact with the genetic material, besides predicting the efficacy and safety in the pharmaceutical industry use as well as in the human health benefit.(AU)

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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 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.; et al. 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, . (12/22364-1, 13/20078-4)

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