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

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.

Paepalanthus spp: antimycobacterial activity of extracts, methoxylated flavonoids and naphthopyranone fractions

Paepalanthus spp., Eriocaulaceae, are native plants from Brazil known as "sempre-vivas" (everlasting flowers). In this work, we evaluated the potential anti-mycobacterial activity of two methoxylated flavonoids (flavonoid 7-methylquercetagetin and 7-methylquercetagetin-4'-O-β-D-glucopyranoside) isolated and identified from P. latipes and the naphthopyranone fractions from P. bromeliodes ethanolic extracts. The MIC value of 500 µg/mL was verified for all compounds tested against M. tuberculosis H37Rv. For M. avium, the MIC value ranged from 1000-2000 µg/mL excepting to naphthopyranone fractions with MIC of 500 µg/mL. This is the first report of activity determination of Paepalanthus spp. flavonoids activity against Mycobacterium tuberculosis and M. avium.

Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

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.

Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata.

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.

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

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.

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

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.

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

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.

Identificaçäo de microbactérias de interesse clínico por cromatografia em camada delgada de micobactina e de ácidos micólicos / Thin-layer chromatography of micobactns and mycolic acids for the identification of clinical mycobacteria

Resumo: Quarenta e sete amostras de micobactérias (12 de referência e 35 isolados de espécimes clínicos) foram analisadas quanto à produçäo de micobactinas e ácidos micólicos, pela técnica de cromatografia em camada delgada (CCD). Diferentes condiçöes de crescimento pouco ou nada afetaram o perfil de separaçäo das micobactinas. Foi verificada a reprodutibilidade nos valores de Rf das micobactinas das diferentes espécies analisadas. Os perfis de ácidos micólicos foram comparados aqueles de amostras padröes. Todaas as amostras da mesma espécie, isoladas de espécimes clínicos, mostraram os mesmos perfis. O uso combinado dos 2 métodos químicos permitiu a identificaçäo das micobactérias patogênicas ou oportunistas cultiváveis. Para o exame de rotina, a análise de micobactinas e de micolatos provêe um meio simples e adequado de caracterizaçäo e identificaçäo de microbactérias (au)

Incidence of mycobacterium tuberculosis and other mycobacteria on pulmonary infections in Araraquara-SP, 1993

Estudou-se a incidência da turberculose e de outras micobacterioses entre os pacientes atendidos no Setor de Tisiologia do Serviço Especial de Saúde de Araraquara-SESA, no ano de 1993. Analisou-se 559 pacientes, verificando-se positivo em 78, dos quais 15 eram simultaneamente portadores do virus da AIDS. Dos 78 casos novos, 69 estavam infectados por M. tuberculosis e outros 9 por micobactérias oportunistas, sendo 5 por M. avium-intracellulare, 2 por M. fortuitum, 1 por M. chelonae e 1 por M. simiae. O isolamento deste último ainda näo havia sido descrito em humanos no Brasil. Verificou-se maior incidência das micobacterioses por micobacterias oportunistas entre os pacientes HIV positivos