Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation.,Journal of Natural Products

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Kendomycin Cytotoxicity against Bacterial, Fungal, and Mammalian Cells Is Due to Cation Chelation.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-03-17 , DOI: 10.1021/acs.jnatprod.9b00826
Dale Tranter ₁ , Ireos Filipuzzi ₂ , Thomas Lochmann ₂ , Britta Knapp ₂ , Juho Kellosalo ₁ , David Estoppey ₂ , Dominik Pistorius ₂ , Axel Meissner ₂ , Ville O Paavilainen ₁ , Dominic Hoepfner ₂

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Kendomycin is a small-molecule natural product that has gained significant attention due to reported cytotoxicity against pathogenic bacteria and fungi as well as a number of cancer cell lines. Despite significant biomedical interest and attempts to reveal its mechanism of action, the cellular target of kendomycin remains disputed. Herein it is shown that kendomycin induces cellular responses indicative of cation stress comparable to the effects of established iron chelators. Furthermore, addition of excess iron and copper attenuated kendomycin cytotoxicity in bacteria, yeast, and mammalian cells. Finally, NMR analysis demonstrated a direct interaction with cations, corroborating a close link between the observed kendomycin polypharmacology across different species and modulation of iron and/or copper levels.

中文翻译：

Kendomycin对细菌，真菌和哺乳动物细胞的细胞毒性归因于阳离子螯合。

Kendomycin是一种小分子天然产物，由于据报道对病原菌和真菌以及许多癌细胞系具有细胞毒性，因此备受关注。尽管有重大的生物医学兴趣并试图揭示其作用机理，但对霉素的细胞靶标仍有争议。在此表明，与已建立的铁螯合剂的作用相比，Kendomycin诱导指示阳离子应激的细胞反应。此外，过量的铁和铜的添加减弱了细菌，酵母和哺乳动物细胞中的霉素的细胞毒性。最后，NMR分析表明与阳离子有直接相互作用，从而证实了观察到的不同物种间的多菌素多药理学与铁和/或铜水平的调节之间的紧密联系。

更新日期：2020-03-17

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