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真菌 Oidiolactones 中的抗真菌 Norditerpene,一种潜在的蝙蝠白鼻综合征生物防治剂。

Antifungal Norditerpene Oidiolactones from the Fungus , a Potential Biocontrol Agent for White-Nose Syndrome in Bats.

机构信息

Center for Drug Design , University of Minnesota , Minneapolis , Minnesota 55405 , United States.

Department of Plant Pathology , University of Minnesota , Minneapolis , Minnesota 55405 , United States.

出版信息

J Nat Prod. 2020 Feb 28;83(2):344-353. doi: 10.1021/acs.jnatprod.9b00789. Epub 2020 Jan 27.

Abstract

White-nose syndrome (WNS) is a devastating disease of hibernating bats caused by the fungus . We obtained 383 fungal and bacterial isolates from the Soudan Iron Mine, an important bat hibernaculum in Minnesota, then screened this library for antifungal activity to develop biological control treatments for WNS. An extract from the fungus was subjected to bioassay-guided fractionation, which led to the isolation of 14 norditerpene and three anthraquinone metabolites. Ten of these compounds were previously described in the literature, and here we present the structures of seven new norditerpene analogues. Additionally, this is the first report of 4-chlorophyscion from a natural source, previously identified as a semisynthetic product. The compounds PR 1388 and LL-Z1271α were the only inhibitors of (MIC = 7.5 and 15 μg/mL, respectively). Compounds were tested for cytotoxicity against fibroblast cell cultures obtained from (northern long eared bat) and (gray bat) using a standard MTT viability assay. The most active antifungal compound, PR 1388, was nontoxic toward cells from both bat species (IC > 100 μM). We discuss the implications of these results in the context of the challenges and logistics of developing a substrate treatment or prophylactic for WNS.

摘要

白鼻综合征(WNS)是一种由真菌引起的冬眠蝙蝠的毁灭性疾病。我们从明尼苏达州苏达州铁矿获得了 383 株真菌和细菌分离株,这是一个重要的蝙蝠冬眠地,然后筛选了这个文库的抗真菌活性,以开发针对 WNS 的生物防治处理方法。从真菌中提取的物质进行了生物测定指导的分离,导致分离出 14 个 norditerpene 和 3 个蒽醌代谢物。其中 10 种化合物以前在文献中有所描述,这里我们介绍了 7 种新的 norditerpene 类似物的结构。此外,这是首次从天然来源中分离出 4-氯physcion,以前被鉴定为半合成产物。化合物 PR 1388 和 LL-Z1271α 是唯一抑制 的抑制剂(MIC = 7.5 和 15 μg/mL)。使用标准的 MTT 活力测定法,测试了化合物对来自 (北方长耳蝙蝠)和 (灰色蝙蝠)的成纤维细胞培养物的细胞毒性。最有效的抗真菌化合物 PR 1388 对两种蝙蝠物种的细胞均无毒性(IC > 100 μM)。我们讨论了这些结果在开发针对 WNS 的基质处理或预防措施的挑战和后勤方面的意义。

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