Wen Han Lin

Bioactive Metabolites from the Endophytic Fungus Stemphylium globuliferum Isolated from Mentha pulegium

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10). The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H (4/5) exhibited considerable cytotoxicity against L5178Y cells with an EC(50) value of 2.7 microg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for kinase inhibitory activity in an assay involving 24 different kinases. Compounds 1, 2, 3, and the mixture of 4 and 5 were the most potent inhibitors, displaying EC(50) values between 0.64 and 1.4 microg/mL toward individual kinases.

Sponge-associated fungi and their bioactive compounds - the Suberites case

Specimens of Suberites domuncula that had been cultured in aquaria for 4 weeks were analyzed for their associated fungi. A total of 81 fungal strains belonging to 20 different genera was isolated and identified by morphological and molecular methods. The most frequently isolated taxa were Cladosporium spp., Penicillium spp., Petriella sp., Phialophora spp. and Engyodontium album. Based on chromatographic and mass spectrometric analysis of fungal extracts, as well as on bioassay results, Aspergillus ustus, Penicillium sp., Petriella sp. and Scopulariopsis sp. were selected for in-depth analysis of their natural products. A total of 19 different fungal metabolites, including three new natural products, was isolated and structurally identified. A. ustus yielded two sesquiterpenes, a drimane derivative and deoxyuvidin, as well as a sesterterpene ophiobolin H. The drimane derivative had an ED50 value against L5178Y cells of 1.9 mu g ml(-1) in vitro. The crude extract of Petriella sp. was also strongly cytotoxic against the L5178Y cell line. The cyclic tetrapeptide WF-3161 was primarily responsible for the activity; the ED50 value was <0.1 mu g ml(-1). It was identical to the known compound WF-3161 and had been previously isolated from Petriella guttulata. In addition to WF-3161, three further natural products were obtained and unequivocally identified as new derivatives of infectopyrone by one-and two-dimensional NMR spectroscopy and by mass spectroscopy. Of the new compounds, only dihydroinfectopyrone was active against L5178Y cells; the ED50 value was 0.2 mu g ml(-1). Penicillium sp. yielded the largest number of metabolites. Viridicatin, viridicatol, cyclopenin and cyclopenol suppressed larval growth of the polyphagous pest insect Spodoptera littoralis when incorporated into an artificial diet at an arbitrarily chosen concentration of 237 ppm. Viridicatol was the most active compound and had an ED50 value of ca. 50 ppm. Scopulariopsis sp. yielded three metabolites, including the known acetylcholinesterase inhibitors quinolactacin A1 and A2.

Cladosporinone, a new viriditoxin derivative from the hypersaline lake derived fungus Cladosporium cladosporioides

A new cytotoxic viriditoxin derivative, cladosporinone (1), along with the known viriditoxin (2) and two viriditoxin derivatives (3 and 4) were obtained from the fungus Cladosporium cladosporioides isolated from the sediment of a hypersaline lake in Egypt. The structure of the new compound (1) was determined by 1D and 2D NMR measurements as well as by high-resolution ESIMS and electronic circular dichroism spectroscopy. All isolated compounds were studied for their cytotoxicity against the murine lymphoma cell line L5187Y and for their antibiotic activity against several pathogenic bacteria. Viriditoxin (2) was the most active compound in both bioassays. Compound 1 also exhibited strong cytotoxicity against the murine lymphoma cell line L5187Y with an IC50 value of 0.88u2009μm, whereas its antibiotic activity was weak.