RESUMEN
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.
Asunto(s)
Hongos/metabolismo , Naftalenos , Compuestos de Espiro , Acetales , Antiinfecciosos , Macrólidos/química , Naftalenos/química , Naftalenos/metabolismo , Compuestos de Espiro/química , Compuestos de Espiro/metabolismoRESUMEN
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).
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Productos Biológicos/aislamiento & purificación , Productos Biológicos/farmacología , Hypocreales/química , Animales , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Productos Biológicos/química , Ensayos de Selección de Medicamentos Antitumorales , Leucemia P388 , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Nueva Zelanda , PeptaibolesRESUMEN
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.
Asunto(s)
Productos Biológicos/química , Técnicas Químicas Combinatorias/métodos , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Técnicas Químicas Combinatorias/economía , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
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.