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Determination of in vitro and in vivo anti-tuberculosis activity of phosphines/diimines Ru (II) complexes

Grant number: 09/06499-1
Support Opportunities:Regular Research Grants
Duration: July 01, 2009 - December 31, 2011
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Clarice Queico Fujimura Leite
Grantee:Clarice Queico Fujimura Leite
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The Mycobacterium tuberculosis, the major agent of tuberculosis (TB), is responsible for approximately 2-3 million people annually death, with a global economic injury of ~$12 billion per year. It is estimated that 1/3 of the worldwide population are infected with the latent form bacilli. Although, no new specific drug against the M. tuberculosis was developed since 1960. It is expected that a new agent against TB, can: (i) to reduce the duration of the treatment time; (ii) to be active against resistant strains; and (iii) to be active against bacilli in latency state. In this project 7 new complexes containing the ruthenium metal (Ru) that have potent activity against TB. Those complexes already had complete chemical assays of synthesis and characterization. The biological assays showed that the high activity of complexes against M. tuberculosis H37Rv is comparable and/or better than that the "first" and "second" line of drugs used for TB treatment. Those complexes also presented a low cytotoxicity against the J774 macrophage culture and intracellular promising activity against M. tuberculosis Erdmann comparable to the rifampicin. Thus, in this project we aimed to determine the in vitro and in vivo pre-clinical profile and to analyze the possibility of the ending of the project to conduct same ones from those seven complexes to the clinical trial. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (5)
(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)
PAVAN, FERNANDO R.; POELHSITZ, GUSTAVO V.; DA CUNHA, LUCAS V. P.; BARBOSA, MARILIA I. F.; LEITE, SERGIO R. A.; BATISTA, ALZIR A.; CHO, SANG H.; FRANZBLAU, SCOTT G.; DE CAMARGO, MARIANA S.; RESENDE, FLAVIA A.; et al. In Vitro and In Vivo Activities of Ruthenium(II) Phosphine/Diimine/Picolinate Complexes (SCAR) against Mycobacterium tuberculosis. PLoS One, v. 8, n. 5, . (11/11593-7, 09/06499-1)
MICHELETTI, ANA CAMILA; HONDA, NELI KIKA; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; CEPA MATOS, MARIA DE FATIMA; PERDOMO, RENATA TRENTIN; BOGO, DANIELLE; ALCANTARA, GLAUCIA BRAZ; BEATRIZ, ADILSON. Increment of Antimycobaterial Activity on Lichexanthone Derivatives. Medicinal Chemistry, v. 9, n. 7, p. 904-910, . (09/06499-1, 08/10390-2)
PAIVA, ISABELA L.; DE CARVALHO, GUSTAVO S. G.; DA SILVA, ADILSON D.; CORBI, PEDRO P.; BERGAMINI, FERNANDO R. G.; FORMIGA, ANDRE L. B.; DINIZ, RENATA; DO CARMO, WEBERTON R.; LEITE, CLARICE Q. F.; PAVAN, FERNANDO R.; et al. Silver(I) complexes with symmetrical Schiff bases: Synthesis, structural characterization, DFT studies and antimycobacterial assays. Polyhedron, v. 62, p. 104-109, . (11/11593-7, 09/06499-1, 12/08230-2)
MONDELLI, MELINA; PAVAN, FERNANDO; DE SOUZA, PAULA C.; LEITE, CLARICE Q.; ELLENA, JAVIER; NASCIMENTO, OTACIRO R.; FACCHIN, GIANELLA; TORRE, MARIA H.. Study of a series of cobalt(II) sulfonamide complexes: Synthesis, spectroscopic characterization, and microbiological evaluation against M. tuberculosis. Crystal structure of [Co( sulfamethoxazole)(2)(H2O)(2)]center dot H2O. Journal of Molecular Structure, v. 1036, p. 180-187, . (11/11593-7, 09/06499-1)
POGGI, MARIANA; BARROSO, RAFAEL; COSTA-FILHO, ANTONIO JOSE; DE BARROS, HELOISA BARBOSA; PAVAN, FERNANDO; LEITE, CLARICE QUEICO; GAMBINO, DINORAH; HELVECIA TORRE, MARIA. New Isoniazid Complexes, Promising Agents Against Mycobacterium tuberculosis. Journal of the Mexican Chemical Society, v. 57, n. 3, p. 198-204, . (11/11593-7, 09/06499-1)

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Filed patent(s) as a result of this research project

PROCESSOS DE PREPARAÇÃO DE COMPLEXOS FOSFÍNICOS DE RUTÊNIO CONTENDO ÍON PICOLINATO E/OU DIIMINAS E/OU BIFOSFINAS EM SUA ESTRUTURA, COMPLEXOS FOSFÍNICOS DE RUTÊNIO OBTIDOS PELOS REFERIDOS PROCESSOS E SEUS USOS PI1001555-8 - Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Universidade Estadual Paulista (UNESP) ; Universidade Federal de São Carlos (UFSCAR) . Clarisse Queico Fujimura Leite ; Alzir Azevedo Batista ; Gustavo Von Poelhsitz ; Marília Imaculada Frazão Barbosa ; Fernando Rogério Pavan - May 2010, 06

METHODS FOR PREPARING RUTHENIUM PHOSPHINE COMPLEXES WITH A STRUCTURE CONTAINING PICOLINATE AND/OR DIIMINE AND/OR BIPHOSPHINE IONS, RUTHENIUM PHOSPHINE COMPLEXES OBTAINED BY THESE METHODS AND USES THEREOF  PCT/BR2011/000151 - Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Universidade Estadual Paulista (UNESP) ; Universidade Federal de São Carlos (UFSCAR) . Clarisse Queico Fujimura Leite ; Alzir Azevedo Batista ; Gustavo Von Poelhsitz ; Marília Imaculada Frazão Barbosa ; Fernando Rogério Pavan - May 2011, 05