Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
J Nat Prod. 2022 Mar 25;85(3):540-546. doi: 10.1021/acs.jnatprod.1c01030. Epub 2022 Jan 31.
The known solid-tumor-selective cytotoxin aulosirazole () was identified from bioactive extracts from the culture medium of the cyanobacterium sp. UIC 10771. Here, we demonstrate that 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 () and C (). Structures for compounds and were determined using HR-ESI-LC-MS/MS and 1D and 2D NMR experiments. Aulosirazoles B () and C () represent the first natural analogues of the FOXO-activating compound aulosirazole () and are the second and third isothiazole-containing metabolites reported from this phylum.
从蓝藻 sp. UIC 10771 的培养物的生物活性提取物中鉴定出已知的实体瘤选择性细胞毒素 aulosirazole()。在这里,我们通过 Western blot 分析和免疫荧光共聚焦显微镜证明,在 OVCAR3 中诱导 FOXO3a 的核积累。我们还报告了另外两种类似物 aulosirazoles B()和 C()的发现。使用 HR-ESI-LC-MS/MS 和 1D 和 2D NMR 实验确定了化合物和的结构。aulosirazoles B()和 C()代表 FOXO 激活化合物 aulosirazole()的第一个天然类似物,并且是该门报告的第二个和第三个含异噻唑的代谢物。