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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 8, n. 5 MAY 28 2013.
• Web of Science Citations: 27

Abstract

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)

• FAPESP's process: 11/11593-7 - Research for new drugs against tuberculosis: laboratory improvement to perform pre-clinical trials
• Grantee: Fernando Rogério Pavan
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/06499-1 - Determination of in vitro and in vivo anti-tuberculosis activity of phosphines/diimines Ru (II) complexes
• Grantee: Clarice Queico Fujimura Leite
• Support Opportunities: Regular Research Grants