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蓝藻 UIC 10771 中的 Aulosirazoles B 和 C:一种异噻唑并萘醌支架的类似物,可在卵巢癌细胞中激活核转录因子 FOXO3a。

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

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.

出版信息

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 () 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.

摘要

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。

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本文引用的文献

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Therapeutic strategies targeting FOXO transcription factors.靶向 FOXO 转录因子的治疗策略。
Nat Rev Drug Discov. 2021 Jan;20(1):21-38. doi: 10.1038/s41573-020-0088-2. Epub 2020 Nov 10.
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FOXO transcription factor family in cancer and metastasis.叉头框转录因子家族与癌症和转移。
Cancer Metastasis Rev. 2020 Sep;39(3):681-709. doi: 10.1007/s10555-020-09883-w.
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Natural Products Containing a Nitrogen-Sulfur Bond.含氮-硫键的天然产物。
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