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1.
J Nat Prod ; 67(12): 2086-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15620258

RESUMO

A screening campaign was implemented utilizing capillary electrophoresis as a primary assay to discover binders to the cancer target Akt1 from a crude natural extract library. Fungal extracts with binding activities were characterized for biochemical inhibition of Akt1 to phosphorylate the downstream substrate protein Bad. One of the crude extracts with bioactivity selected for isolation and structure elucidation from fermentation of the fungal culture Oidiodendron sp. F01895 yielded a new trihydroxy phthalide (1). The structure of 1 was determined by a combination of 1D and 2D NMR spectroscopic data along with high-resolution mass spectrometric data. Compound 1 displays inhibition of Akt1 biochemical activity in vitro and confers growth inhibition on some cancer-derived cell lines in culture.


Assuntos
Antineoplásicos/isolamento & purificação , Benzofuranos/isolamento & purificação , Fungos/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Proteínas Proto-Oncogênicas c-akt , Células Tumorais Cultivadas
2.
J Antibiot (Tokyo) ; 55(10): 899-903, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12523823

RESUMO

Random subsets of a modest-sized microbial collection have been examined for culture redundancy, initially by morphology, both to the naked eye and microscopically, of cultures grown on a variety of agar-based solid media. Subsequent analysis, by simple TLC, of the extractable metabolites produced by morphologically similar cultures grown in submerged shaken fermentation was carried out. Apparent duplicate cultures were further examined on Biolog SF-P MicroPlates for differentiation. The results were subjected to a statistical analysis and the contribution of each stage in the process to resolving culture uniqueness was noted. A statistical extrapolation of the results, from the subsets of each culture type, to the total for that type within the entire collection, with 95% confidence limits, is presented. Morphological comparison, on four different agar media, gives a significant underestimation of the metabolic diversity of the collection. The weighted mean from the three types of cultures indicate that the expected content of the collection is approximately 93% unique strains.


Assuntos
Actinobacteria/classificação , Fungos/classificação , Actinobacteria/metabolismo , Fungos/metabolismo
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