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Determination of pre-clinical profile in vitro and in vivo anti-tuberculosis activity of ruthenium(II)phosphine / picolinate complexes

Grant number: 08/10390-2
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2009
Effective date (End): November 30, 2011
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Clarice Queico Fujimura Leite
Grantee:Fernando Rogério Pavan
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

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) reduce the duration of the treatment time; (II) be active against resistant strains; and (III) be active against bacilli in latency state. In this project 7 new complexes containing the ruthenium metal (Ru) that have potent activity against TB are presented. 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)

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Scientific publications (13)
(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)
COELHO, ROBERTA GOMES; HONDA, NELI KIKA; VIEIRA, MARIA DO CARMO; BRUM, ROSENEI LOUZADA; PAVAN, FERNANDO ROGERIO; FUJIMURA LEITE, CLARICE QUEICO; LIMA CARDOSO, CLAUDIA ANDREA. Chemical Composition and Antioxidant and Antimycobacterial Activities of Bromelia balansae (Bromeliaceae). JOURNAL OF MEDICINAL FOOD, v. 13, n. 5, p. 1277-1280, . (08/10390-2)
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)
CARMO, ARTURENE M. L.; SILVA, FLAVIA M. C.; MACHADO, PATRICIA A.; FONTES, ANA P. S.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; LEITE, SERGIO R. DE A.; COIMBRA, ELAINE S.; DA SILVA, ADILSON D.. Synthesis of 4-aminoquinoline analogues and their platinum(II) complexes as new antileishmanial and antitubercular agents. BIOMEDICINE & PHARMACOTHERAPY, v. 65, n. 3, p. 204-209, . (08/10390-2)
MOREIRA, RAQUEL R. D.; MARTINS, GILMARCIO Z.; PIETRO, ROSEMEIRE C. L. R.; SATO, DAISY N.; PAVAN, FERNANDO R.; LEITE, SERGIO R. A.; VILEGAS, WAGNER; LEITE, CLARICE Q. F.. Paepalanthus spp: Antimycobacterial activity of extracts, methoxylated flavonoids and naphthopyranone fractions. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 23, n. 2, p. 268-272, . (11/11593-7, 08/10390-2)
SANTOS, JEAN L.; YAMASAKI, PAULO R.; CHIN, CHUNG MAN; TAKASHI, CELIO H.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.. Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives. Bioorganic & Medicinal Chemistry, v. 17, n. 11, p. 3795-3799, . (07/56115-0, 08/10390-2)
GAMBINO, DINORAH; FERNANDEZ, MARIANA; SANTOS, DIEGO; ETCHEVERRIA, GUSTAVO A.; PIRO, OSCAR E.; PAVAN, FERNANDO R.; LEITE, CLARICE Q. F.; TOMAZ, ISABEL; MARQUES, FERNANDA. Searching for gallium bioactive compounds: Gallium(III) complexes of tridentate salicylaldehyde semicarbazone derivatives. Polyhedron, v. 30, n. 7, p. 1360-1366, . (08/10390-2)
PAVAN, FERNANDO R.; DE CARVALHO, GUSTAVO SENRA G.; DA SILVA, ADILSON D.; LEITE, CLARICE Q. F.. Synthesis and Anti-Mycobacterium tuberculosis Evaluation of Aza-Stilbene Derivatives. SCIENTIFIC WORLD JOURNAL, v. 11, p. 1113-1119, . (08/10390-2)
DE PRINCE, KARINA ANDRADE; SORDI, RENATA; PAVAN, FERNANDO ROGERIO; BARRETO SANTOS, ADOLFO CARLOS; ARAUJO, ANGELA R.; LEITE, SERGIO R. A.; LEITE, CLARICE Q. F.. ANTI-MYCOBACTERIUM TUBERCULOSIS ACTIVITY OF FUNGUS PHOMOPSIS STIPATA. Brazilian Journal of Microbiology, v. 43, n. 1, p. 224-229, . (11/11593-7, 08/10390-2)
PAVAN, FERNANDO R.; POELHSITZ, GUSTAVO V.; BARBOSA, MARILIA I. F.; LEITE, SERGIO R. A.; BATISTA, ALZIR A.; ELLENA, JAVIER; SATO, LETICIA S.; FRANZBLAU, SCOTT G.; MORENO, VIRTUDES; GAMBINO, DINORAH; et al. Ruthenium(II) phosphine/diimine/picolinate complexes: Inorganic compounds as agents against tuberculosis. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 46, n. 10, p. 5099-5107, . (08/10390-2)
MIYATA, MARCELO; PAVAN, FERNANDO ROGERIO; SATO, DAISY NAKAMURA; MARINO, LEONARDO BIANCOLINO; HIRATA, MARIO HIROYUKI; CARDOSO, ROSILENE FRESSATI; FIUZA DE MELO, FERNANDO AUGUSTO; ZANELLI, CLESLEI FERNANDO; FUJIMURA LEITE, CLARICE QUEICO. Drug resistance in Mycobacterium tuberculosis clinical isolates from Brazil: Phenotypic and genotypic methods. BIOMEDICINE & PHARMACOTHERAPY, v. 65, n. 6, p. 456-459, . (08/10390-2)
PAVAN, FERNANDO R.; VON POELHSITZ, GUSTAVO; DO NASCIMENTO, FABIO B.; LEITE, SERGIO R. A.; BATISTA, ALZIR A.; DEFLON, VICTOR M.; SATO, DAISY N.; FRANZBLAU, SCOTT G.; LEITE, CLARICE Q. F.. Ruthenium (II) phosphine/picolinate complexes as antimycobacterial agents. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 45, n. 2, p. 598-601, . (08/10390-2)
PAVAN, FERNANDO R.; MAIA, PEDRO I. DA S.; LEITE, SERGIO R. A.; DEFLON, VICTOR M.; BATISTA, ALZIR A.; SATO, DAISY N.; FRANZBLAU, SCOTT G.; LEITE, CLARICE Q. F.. Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 45, n. 5, p. 1898-1905, . (08/10390-2)
FERNANDO ROGÉRIO PAVAN; CLARICE QUEICO FUJIMURA LEITE; ROBERTA GOMES COELHO; ISABEL DUARTE COUTINHO; NELI KIKA HONDA; CLAUDIA ANDRÉA LIMA CARDOSO; WAGNER VILEGAS; SERGIO ROBERTO DE ANDRADE LEITE; DAISY NAKAMURA SATO. Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae). Química Nova, v. 32, n. 5, p. 1222-1226, . (08/10390-2, 02/05503-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PAVAN, Fernando Rogério. Determinação do perfil pré-clínico da atividade anti-tuberculose in vitro e in vivo de complexos heterolépticos de Rutênio(II) com fosfinas. diiminas e picolinato como ligantes. 2011. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.

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