Aulosirazoles B and C from the Cyanobacterium Nostoc sp. UIC10771: Analogues of an Isothiazolonaphthoquinone Scaffold that Activate Nuclear Transcription Factor FOXO3a in Ovarian Cancer Cells br

The known solid-tumor-selective cytotoxin aulosirazole (1) was identified from bioactive extracts from the culture medium of the cyanobacterium Nostocsp. UIC10771. Here, we demonstrate that1induces the nuclear accumulation of FOXO3a inOVCAR3 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 compounds2and3were 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 thesecond and third isothiazole-containing metabolites reported from this phylum.