Aulosirazoles B and C from the Cyanobacterium Nostoc sp. UIC 10771: Analogues of an Isothiazolonaphthoquinone Scaffold that Activate Nuclear Transcription Factor FOXO3a in Ovarian Cancer Cells.

The known solid-tumor-selective cytotoxin aulosirazole ( 1 ) was identified from bioactive extracts from the culture medium of the cyanobacterium Nostoc sp. UIC 10771. Here, we demonstrate that 1 induces the nuclear accumulation of FOXO3a in OVCAR3 using both Western blot analysis and immunofluorescence confocal microscopy. We also report the discovery of two additional analogues, aulosirazoles B ( 2 ) and C ( 3 ). Structures for compounds 2 and 3 were determined using HR-ESI-LC-MS/MS and 1D and 2D NMR experiments. Aulosirazoles B ( 2 ) and C ( 3 ) represent the first natural analogues of the FOXO-activating compound aulosirazole ( 1 ) and are the second and third isothiazole-containing metabolites reported from this phylum.