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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antitubercular Agents / adverse effects
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Antitubercular Agents / chemical synthesis
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology*
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Coordination Complexes / chemical synthesis
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology*
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Drug Resistance, Bacterial / drug effects
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Female
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Humans
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Imines / chemical synthesis
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Imines / chemistry
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Imines / pharmacology*
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Mice
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Mice, Inbred C57BL
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Microbial Sensitivity Tests
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Mutagenesis / drug effects
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Mutagenicity Tests
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / isolation & purification
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Phosphines / chemical synthesis
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Phosphines / chemistry
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Phosphines / pharmacology*
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Picolinic Acids / chemical synthesis
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Picolinic Acids / chemistry
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Picolinic Acids / pharmacology*
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Ruthenium / chemistry
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Ruthenium / pharmacology*
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Toxicity Tests, Acute
Substances
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Antitubercular Agents
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Coordination Complexes
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Imines
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Phosphines
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Picolinic Acids
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Ruthenium
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phosphine
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picolinic acid
Grants and funding
This study was supported by CNPq, PROEX and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ref. Process: 2011/11593-7 and 2009/06499-1 and CYTED-RIIDFCM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.