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克拉多辛 L-O,来自内生真菌枝孢属 WBS017 的新型杂合聚酮。

Cladosins L-O, new hybrid polyketides from the endophytic fungus Cladosporium sphaerospermum WBS017.

机构信息

Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany; Department of Production of Special Utilized Plant, Agronomy College, Sichuan Agricultural University, No. 211, Huimin Rd, Wenjiang Region, Chengdu, 611130, Sichuan, PR China; Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Research Center for Medicine & Biology, Zunyi Medical University, Zunyi, 563000, Guizhou, PR China.

Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany; Department of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519, Minia, Egypt.

出版信息

Eur J Med Chem. 2020 Apr 1;191:112159. doi: 10.1016/j.ejmech.2020.112159. Epub 2020 Feb 19.

Abstract

The endophytic fungus Cladosporium sphaerospermum WBS017 was obtained from healthy bulbs of Fritillaria unibracteata var. wabuensis. Fermentation of C. sphaerospermum on solid rice medium yielded three new hybrid polyketides, cladosins L-N (1-3), and a known derivative cladodionen (4). Further cultivation of this fungus on white bean medium afforded an additional new hybrid polyketide, cladosin O (5) along with three known analogues (6-8). The structures of the new compounds were elucidated using a combination of NMR and HRESIMS data. The absolute configurations of compounds 2 and 3 were determined by Mosher's method and TDDFT-ECD calculations. All isolated compounds were evaluated for their cytotoxic and antimicrobial activities. Cladodionen (4) exhibited cytotoxicity against the mouse lymphoma cell line L5178Y with an IC value of 3.7 μM, and also exhibited antifungal activity against Ustilago maydis and Saccharomyces cerevisiae, while cladosin L (1) displayed week antibacterial activity against Staphylococcus aureus ATCC 29213 and S. aureus ATCC 700699 with MIC values of 50 and 25 μM, respectively.

摘要

从健康的宝铎百合鳞茎中获得内生真菌枝孢属 sphaerospermum WBS017。枝孢属 sphaerospermum 在固体大米培养基上发酵产生三种新的杂种聚酮化合物,cladosins L-N(1-3),以及一种已知的衍生物 cladodionen(4)。进一步在白豆培养基上培养这种真菌,得到了一种新的杂种聚酮化合物 cladosin O(5),以及三种已知的类似物(6-8)。新化合物的结构通过 NMR 和 HRESIMS 数据的组合来阐明。通过 Mosher 法和 TDDFT-ECD 计算确定了化合物 2 和 3 的绝对构型。所有分离得到的化合物都进行了细胞毒性和抗菌活性评价。Cladodionen(4)对 L5178Y 小鼠淋巴瘤细胞系具有细胞毒性,IC 值为 3.7 μM,对玉米黑粉菌和酿酒酵母也具有抗真菌活性,而 cladosin L(1)对金黄色葡萄球菌 ATCC 29213 和金黄色葡萄球菌 ATCC 700699 具有较弱的抗菌活性,MIC 值分别为 50 和 25 μM。

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