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A series of novel drimane sesquiterpene esters (1-6) was isolated from fermentations of Aspergillus ustus var. pseudodeflectus and their structures elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The major component of the fermentation, 1, was (2'E,4'E,6'E)-6-(1'-carboxy-2',4',6'-trien)-9-hydroxydrim-7-ene-11 ,12-olide. Compounds 1, 2, 3 and 5 exhibited endothelin receptor binding inhibitory activity against rabbit endothelin-A and rat endothelin-B receptors with IC50 values in the range 20-150 microM. These compounds had similar levels of activity in assays for binding to human endothelin A and endothelin B receptors. The isolation of 9,11-dihydroxy-6-oxodrim-7-ene, 7, a probable biosynthetic precursor to the drimane esters is also reported.

Xenovulene A, a novel inhibitor of benzodiazepine binding to the GABA-benzodiazepine receptor is produced by submerged fermentation of Acremonium strictum. It was isolated from the mycelium by solvent extraction and purified by chromatography on Sephadex LH-20 and octadecyl silica. The structure of xenovulene A was determined to be a novel oxygenated sesquiterpene containing a humulene moiety by interpretation of various spectroscopic data, especially from 2D NMR experiments. Xenovulene A inhibited binding of the benzodiazepine, flunitrazepam, with an IC50 of 40 nM in an in vitro assay using bovine synaptosome membrane preparations.

A series of reduced benzo[j]fluoranthen-3-ones (1-4) was isolated from fermentations of a fungal strain CBUK20700 (CBS 100220), classified as Cladosporium cf. cladosporioides, during a microbial extract screening programme to identify inhibitors of anti-CD2 8-induced interleukin-2 (IL-2) production by Jurkat E6-1 cells as potential immunosuppressive agents. These compounds were also found to be tyrosine kinase inhibitors. The structures of compounds 1-4 were elucidated by spectroscopic methods including the HMQC, HMBC and NOESY NMR experiments. The most potent compound in the series, (6bS, 7R, 8S)-7-methoxy-4, 8, 9-trihydroxy-1, 6b, 7, 8-tetrahydro-2H-benzo[j]fluoranthen-3-one (1) inhibited anti-CD28-induced IL-2 production and Abl tyrosine kinase with IC50 values of 400 and 60 nM respectively. The 6b-stereoisomeric 2 was a moderate inhibitor of both IL-2 production and Abl tyrosine kinase while the 8-oxo derivative 3 was inactive in both assays. The 8-O-methyl ether 4 was a moderate inhibitor of IL-2 production but exhibited potent inhibition of Abl tyrosine kinase with an IC50 of 45 nM.