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, (6b
S, 7
R, 8
S)-7-methoxy-4, 8, 9-trihydroxy-1, 6b, 7, 8-tetrahydro-2
H-benzo[j]fluoranthen-3-one (
1) inhibited anti-CD28-induced IL-2 production and Abl tyrosine kinase with IC
50 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 IC
50 of 45 nM.
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