In Vitro and In Vivo Activities of Ruthenium(II) Phosphine/Diimine/Picolinate Complexes (SCAR) against Mycobacterium tuberculosis

Autor(es):Mostrar menos -

Pavan, Fernando R. ^[1] ; Poelhsitz, Gustavo V. ^[2] ; da Cunha, Lucas V. P. ^[3] ; Barbosa, Marilia I. F. ^[3] ; Leite, Sergio R. A. ^[4] ; Batista, Alzir A. ^[3] ; Cho, Sang H. ^[3] ; Franzblau, Scott G. ^[5] ; de Camargo, Mariana S. ^[1] ; Resende, Flavia A. ^[1] ; Varanda, Eliana A. ^[1] ; Leite, Clarice Q. F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Paulista, Coll Pharm, Dept Biol Sci, Araraquara, SP - Brazil

^[2] Univ Fed Uberlandia, Inst Chem, BR-38400 Uberlandia, MG - Brazil

^[3] Univ Fed Sao Carlos, Dept Chem, BR-13560 Sao Carlos, SP - Brazil

^[4] Univ Estadual Paulista, Inst Chem, Araraquara, SP - Brazil

^[5] Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL - USA

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 5 MAY 28 2013.
• Citações Web of Science: 27

Resumo

Rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class form part of a 6-month regimen that is ineffective against MDR and XDR TB, and incompatible with many antiretroviral drugs. Investments in R\&D strategies have increased substantially in the last decades. However, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. Ruthenium complexes (SCAR) have been tested in our laboratory and showed promising activity against Mycobacterium tuberculosis. These complexes showed up to 150 times higher activity against MTB than its organic molecule without the metal (free ligand), with low cytotoxicity and high selectivity. In this study, promising results inspired us to seek a better understanding of the biological activity of these complexes. The in vitro biological results obtained with the SCAR compounds were extremely promising, comparable to or better than those for first-line drugs and drugs in development. Moreover, SCAR 1 and 4, which presented low acute toxicity, were assessed by Ames test, and results demonstrated absence of mutagenicity. (AU)

• Processo FAPESP: 11/11593-7 - Pesquisa de novos fármacos contra tuberculose: implementação laboratorial para realizar ensaios pré-clínicos
• Beneficiário: Fernando Rogério Pavan
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/06499-1 - Determinação da atividade anti-tuberculose in vitro e in vivo de complexos de Ru(II) fosfinas/diiminas
• Beneficiário: Clarice Queico Fujimura Leite
• Modalidade de apoio: Auxílio à Pesquisa - Regular