Wortmannin and Wortmannine Analogues from an Undescribed Niesslia sp.

Wortmannin and Wortmannine Analogues from an Undescribed Niesslia sp.
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DOI:
10.1021/acs.jnatprod.8b00923
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发表时间:
2019-03
影响因子:
5.1
通讯作者:
N. M. Dischler;Lijian Xu;Yan Li;Connie B Nichols;J. Alspaugh;G. Bills;J. Gloer
N. M. Dischler;Lijian Xu;Yan Li;Connie B Nichols;J. Alspaugh;G. Bills;J. Gloer
中科院分区:
生物学2区
文献类型:
--
作者:
N. M. Dischler;Lijian Xu;Yan Li;Connie B Nichols;J. Alspaugh;G. Bills;J. Gloer

文献摘要

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在我们研究粪真菌作为抗真菌剂来源的过程中,从德克萨斯州收集的马粪中分离出一种未描述的尼斯菌属菌株(TTI-0426)。该菌株发酵培养物的提取物提供了两种新的抗真菌渥曼青霉素衍生物,渥曼青霉素 C 和 D(1 和 2),以及另外四种新的相关化合物,渥曼青霉素 B1-B4 (3-6),含有不寻常的环系统。这些代谢物的结构主要通过 HRESIMS 和 2D NMR 数据分析来确定。使用 NOESY 数据指定相对构型,并且通过与类似化合物的 NMR 比较来支持结构指定。渥曼青霉素 C 和 D 在纸盘测定中显示出针对新型隐球菌和白色念珠菌的活性,但根据与野生型相比的粟酒裂殖酵母外排突变体的测定结果,认为 1 观察到的低 MIC 效力部分是由于外排过程所致。
In the course of our studies of coprophilous fungi as sources of antifungal agents, a strain of an undescribed species in the genus Niesslia (TTI-0426) was isolated from horse dung collected in Texas. An extract from fermentation cultures of this strain afforded two new antifungal wortmannin derivatives, wortmannins C and D (1 and 2), as well as four additional new related compounds, wortmannines B1-B4 (3-6), containing an unusual ring system. The structures of these metabolites were established mainly by analysis of HRESIMS and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. Wortmannins C and D showed activity against Cryptococcus neoformans and Candida albicans in disk assays, but low MIC potency observed for 1 was suggested to be due in part to efflux processes on the basis of assay results for a Schizosaccharomyces pombe efflux mutant in comparison to wild-type.