Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Bioorg Med Chem Lett ; 24(3): 870-9, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24405701

RESUMO

Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC=0.1 µM) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration.


Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Piridonas/síntese química , Tiazóis/síntese química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia , Ureia/síntese química , Ureia/farmacologia , Administração Oral , Animais , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Modelos Animais de Doenças , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piridonas/química , Piridonas/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Inibidores da Topoisomerase II/química , Ureia/química
2.
Antimicrob Agents Chemother ; 56(6): 3054-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22470118

RESUMO

Coadministration of moxifloxacin and rifampin was evaluated in a murine model of Mycobacterium tuberculosis pulmonary infection to determine whether the finding of antagonism documented in a hollow-fiber infection model could be recapitulated in vivo. Colony counts were followed in a no-treatment control group, groups administered moxifloxacin or rifampin monotherapy, and a group administered a combination of the two agents. Following 18 days of once-daily oral administration to mice infected with M. tuberculosis, there was a reduction in the plasma exposure to rifampin that decreased further when rifampin was coadministered with moxifloxacin. Pharmacodynamic analysis demonstrated a mild antagonistic interaction between moxifloxacin and rifampin with respect to cell kill in the mouse model for tuberculosis (TB). No emergence of resistance was noted over 28 days of therapy, even with monotherapy. This was true even though one of the agents in the combination (moxifloxacin) induces error-prone replication. The previously noted antagonism with respect to cell kill shown in the hollow-fiber infection model was recapitulated in the murine TB lung model, although to a lesser extent.


Assuntos
Antituberculosos/uso terapêutico , Compostos Aza/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Quinolinas/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Compostos Aza/administração & dosagem , Compostos Aza/farmacocinética , Fluoroquinolonas , Camundongos , Camundongos Endogâmicos BALB C , Moxifloxacina , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Rifampina/administração & dosagem , Rifampina/farmacocinética , Tuberculose Pulmonar/microbiologia
3.
Indian J Med Res ; 132: 62-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20693591

RESUMO

BACKGROUND & OBJECTIVES: Several studies reported the polymorphisms of beta1-adrenergic receptor gene in healthy volunteers and its influence on cardiovascular disorders. We investigated the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism in healthy volunteers of South Indian Tamilian population vis-à-vis other major ethnic groups. METHODS: The genetic variants were determined by using Taqman 5' nuclease assay- real time PCR analysis in 533 normal healthy volunteers (18-60 yr; M=290; F=243). The allelic discrimination analysis was done by 7700 SDS software. RESULTS: The estimated genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared with other major populations. The frequencies of the variant alleles Gly49 and Gly389 were 15.1 and 25.8 per cent respectively. INTERPRETATION & CONCLUSIONS: Our study shows that interethnic variation exists in the polymorphisms of beta1-adrenergic receptor gene and the results generated in this study might serve as a genetic marker for further studies in Tamilian (South India) population.


Assuntos
Etnicidade/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 1/genética , Adulto , Substituição de Aminoácidos/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...