RESUMO
Biosynthetic studies on spiro-mamakone A (1), a potently cytotoxic and antimicrobial compound from an endophytic fungus isolated from the New Zealand native tree Knightia excelsa (rewarewa), confirm the polyketide origins of this unique compound belonging to the spirobisnaphthalene class of compounds. The biosynthesis proceeds via an unprecedented symmetric enedione with the two halves of the molecule being formed from two separate pentaketide units connected by oxidative coupling.
Assuntos
Fungos/metabolismo , Naftalenos , Compostos de Espiro , Acetais , Anti-Infecciosos , Macrolídeos/química , Naftalenos/química , Naftalenos/metabolismo , Compostos de Espiro/química , Compostos de Espiro/metabolismoRESUMO
The use of an HPLC bioactivity profiling/microtiter plate technique in conjunction with capillary probe NMR instrumentation and access to appropriate databases effectively short-circuits conventional dereplication procedures, necessarily based on multimilligram extracts, to a single, more rapid submilligram operation. This approach to dereplication is illustrated using fungal or bacterial extracts that contain known compounds. In each case the dereplication steps were carried out on microgram quantities of extract and demonstrate the discriminating power of (1)H NMR spectroscopy as a definitive dereplication tool.
Assuntos
Produtos Biológicos/química , Técnicas de Química Combinatória/métodos , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Técnicas de Química Combinatória/economia , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
By the application of an HPLC bioactivity profiling/microtiter technique in conjunction with capillary NMR instrumentation and access to the AntiMarin database the conventional evaluation/isolation dereplication/characterization procedures can be dramatically truncated. This approach is illustrated using the isolation of a new peptaibol, chrysaibol (1), from a New Zealand isolate of the mycoparasitic fungus Sepedonium chrysospermum. The unique nature of chrysaibol was recognized by bioactivity-guided fractionation using HPLC bioactivity profiling/microtiter plate analysis in conjunction with capillary NMR instrumentation and the AntiMarin database. 2D NMR techniques, in combination with MS fragmentation experiments, determined the planar structure of chrysaibol (1), while the absolute configurations of the amino acid residues were defined by Marfey's method. Chrysaibol (1) was cytotoxic against the P388 murine leukemia cell line (IC50 6.61 microM) and showed notable activity against Bacillus subtilis (IC50 1.54 microM).
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Hypocreales/química , Animais , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Produtos Biológicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388 , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nova Zelândia , PeptaibolsRESUMO
Using HPLC/microtiter-plate-based generation of activity profiles the extract of a marine alga-derived fungus, identified as Gliocladium sp., was shown to contain the known strongly cytotoxic metabolite 4-keto-clonostachydiol (1) and also clonostachydiol (2) as well as gliotide (3), a new cyclodepsipeptide containing several D-amino acids. The absolute configuration of 1 was elucidated by reduction to 2, and two further oxidized derivatives of clonostachydiol (5, 6) were prepared and evaluated for biological activity.
