Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides
Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides
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DOI：
10.1038/ja.2010.110
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Takemoto, Jon Y.
中科院分区：
文献类型：
--
作者：
Chang, Cheng-Wei T.;Fosso, Marina;Takemoto, Jon Y.
许多放线菌都是广泛使用的氨基糖苷类抗生素。虽然主要是抗菌药物，但一些已知的氨基糖苷类化合物也对酵母菌、原生动物和重要的作物病原真菌卵菌有抑制作用。在这里，我们展示了将C8烷基链连接到基于新胺的氨基糖苷类化合物的III环上，特别是在4‘’-O位产生了一种广谱杀菌剂(FG08)，而没有氨基糖苷类化合物的典型抗菌性能。叶片侵染分析和温室研究表明，FG08能够在植物毒性最低的浓度下抑制小麦赤霉病病原菌--禾谷镰刀菌对小麦的侵染。与典型的核糖体蛋白翻译错误的氨基糖苷作用不同，FG08‘S的抗真菌作用涉及质膜的扰动。这种从抗菌到抗真菌的转化可能为开发适合于作物病害应用的新型氨基糖苷类杀菌剂铺平道路。此外，这一策略是通过简单的化学修饰来复兴临床上过时的药物以产生新应用的一个例子。《抗生素杂志》(2010年)63667672；doi：10.1038/ja.2010.110；10月6日在线发布
Many Actinomycetes aminoglycosides are widely used antibiotics. Although mainly antibacterials, a few known aminoglycosides also inhibit yeasts, protozoans and important crop pathogenic fungal oomycetes. Here we show that attachment of a C8 alkyl chain to ring III of a neamine-based aminoglycoside specifically at the 4 ''-o position yields a broad-spectrum fungicide (FG08) without the antibacterial properties typical for aminoglycosides. Leaf infection assays and greenhouse studies show that FG08 is capable of suppressing wheat fungal infections by Fusarium graminearurn-the causative agent of Fusarium head blight-at concentrations that are minimally phytotoxic. Unlike typical aminoglycoside action of ribosomal protein translation miscoding, FG08's antifungal action involves perturbation of the plasma membrane. This antibacterial to antifungal transformation could pave the way for the development of a new class of aminoglycoside-based fungicides suitable for use in crop disease applications. In addition, this strategy is an example of reviving a clinically obsolete drug by simple chemical modification to yield a new application. The Journal of Antibiotics (2010) 63, 667-672; doi:10.1038/ja.2010.110; published online 6 October 2010