Publications by authors named "Sergio R A Leite"

6 Publications

  • Page 1 of 1

In vitro and in vivo activities of ruthenium(II) phosphine/diimine/picolinate complexes (SCAR) against Mycobacterium tuberculosis.

PLoS One 2013 28;8(5):e64242. Epub 2013 May 28.

Department of Biological Sciences, College of Pharmacy, Univ Estadual Paulista, Araraquara, São Paulo, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064242PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665843PMC
January 2014

Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata.

Braz J Microbiol 2012 Jan 1;43(1):224-9. Epub 2012 Jun 1.

Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista , Araraquara, SP , Brasil ; Faculdades Integradas Pitágoras , Montes Claros, MG , Brasil.

Our purpose was to determine the anti-Mycobacterium tuberculosis activity of the metabolites produced by the endophitic fungus Phomopsis stipata (Lib.) B. Sutton, (Diaporthaceae), cultivated in different media. The antimycobacterial activity was assessed through the Resazurin Microtiter Assay (REMA) and the cytotoxicity test performed on macrophage cell line. The extracts derived from fungi grown on Corn Medium and Potato Dextrose Broth presented the smallest values of Minimum Inhibitory Concentration (MIC) and low cytotoxicity, which implies a high selectivity index. This is the first report on the chemical composition and antitubercular activity of metabolites of P. stipata, as well as the influence of culture medium on these properties.
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http://dx.doi.org/10.1590/S1517-838220120001000024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769001PMC
January 2012

Ruthenium(II) phosphine/diimine/picolinate complexes: inorganic compounds as agents against tuberculosis.

Eur J Med Chem 2011 Oct 23;46(10):5099-107. Epub 2011 Aug 23.

Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, CEP 14801-902, Araraquara, SP, Brazil.

This paper describes the synthesis and characterization of four new ruthenium complexes containing 1,4 bis(diphenylphosphino)butane (dppb), 2-pyridinecarboxylic acid anion (pic) and the diimines [(2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me-bipy), 4,4'-dichloro-2,2'-bipyridine (Cl-bipy) and 1,10-phenanthroline (phen) as ligands, with formulae [Ru(pic)(dppb)(bipy)]PF(6) (SCAR01), [Ru(pic)(dppb)(Me-bipy)]PF(6) (SCAR02), [Ru(pic)(dppb)(Cl-bipy)]PF(6) (SCAR03) and [Ru(pic)(dppb)(phen)]PF(6) (SCAR04). Additionally, the in vitro anti-Mycobacterium tuberculosis (MTB) activity, cytotoxicity and activity against in vitro infection of these complexes and two more complexes, cis-[Ru(pic)(dppe)(2)]PF(6) (SCAR05) and cis-[RuCl(2)(dppb)(bipy)] (SCAR06), and their free ligands are described and discussed. All compounds showed excellent MIC against MTB, low cytotoxicity and a selectivity index higher than 10. Also, all compounds showed significant intracellular inhibition and the compound SCAR05 showed a better activity than rifampin and SQ109. This is the first report of activity against in vitro infection of ruthenium compounds.
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http://dx.doi.org/10.1016/j.ejmech.2011.08.023DOI Listing
October 2011

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: anti-Mycobacterium tuberculosis activity and cytotoxicity.

Eur J Med Chem 2010 May 28;45(5):1898-905. Epub 2010 Jan 28.

Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14801-902 Araraquara, SP, Brazil.

The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC50) was determined to establish a selectivity index (SI) (SI=IC50/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of "first line" or "second line" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates.
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http://dx.doi.org/10.1016/j.ejmech.2010.01.028DOI Listing
May 2010

Screening of molecules with anti-TB activity from the brazilian cerrado plants.

Rev Port Pneumol 2010 Jan;16SA:S83-8

Faculdade de Ciências Farmacêuticas, UNESP, CEP 14801-902, Araraquara (SP), Brasil. Electronic address:

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http://dx.doi.org/10.1016/S0873-2159(15)30097-0DOI Listing
January 2010

Ruthenium (II) phosphine/picolinate complexes as antimycobacterial agents.

Eur J Med Chem 2010 Feb 6;45(2):598-601. Epub 2009 Nov 6.

Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, CEP 14801-902, Araraquara, SP, Brazil.

The synthesis, characterization and the anti-Mycobacterium tuberculosis (MTB) activities of three ruthenium complexes containing the 2-pyridinecarboxylic acid anion (picolinate), with formulae cis- [Ru(pic)(dppm)(2)]PF(6) (1), cis- [Ru(pic)(dppe)(2)]PF(6) (2) and [Ru(pic)(2)(PPh(3))(2)] (3) [pic=2-pyridinecarboxylate; dppm=bis(diphenylphosphino)methane; dppe=1,2-bis(diphenylphosphino)ethane; PPh(3)=triphenylphosphine] are reported in this article. The complexes were characterized by elemental analysis, spectroscopic and electrochemical techniques. Their in vitro antimycobacterial activity was determinated as the Minimum Inhibitory Concentration (MIC) for MTB cell growth, measured by the REMA method. The best MICs were found for complexes (1) and (2), with values of 0.78 and 0.26 microg/mL, respectively. The results are comparable to or better than "first line" or "second line" drugs commonly used in the treatment of TB.
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http://dx.doi.org/10.1016/j.ejmech.2009.10.049DOI Listing
February 2010
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