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

J Nat Prod. 2022 Mar 25;85(3):540-546. doi: 10.1021/acs.jnatprod.1c01030. Epub 2022 Jan 31.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Female
  • Humans
  • Nostoc* / chemistry
  • Ovarian Neoplasms* / drug therapy
  • Tandem Mass Spectrometry
  • Transcription Factors

Substances

  • Transcription Factors