Brominated Azaphilones from the Sponge-Associated Fungus Penicillium canescens Strain 4.14.6a
Brominated Azaphilones from the Sponge-Associated Fungus Penicillium canescens Strain 4.14.6a
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DOI：
10.1021/acs.jnatprod.9b00151
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发表时间：
2019-08-01
影响因子：
5.1
通讯作者：
Proksch, Peter
中科院分区：
文献类型：
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作者：
Frank, Marian;Hartmann, Rudolf;Proksch, Peter
从地中海海绵Agelas oroides的内部组织中分离到真菌Penicillium canescens。该菌在固体大米培养基上发酵产生一个新的氯代二苯醚（1）和13个已知化合物（2-14）。在水稻培养基中添加5%NaBr增加了4-6的量，同时降低了8、12和14的量。此外，它还诱导了17种和两种新的溴化氮杂菲酮（溴菲酮A和溴菲酮B）的积累（15和16）。化合物15和16是具有通过亚甲基连接的苯部分和吡喃醌核的氮杂菲酮的第一个实例。新化合物的结构根据1D和2D NMR谱以及HRESIMS数据进行了鉴定。通过sTDA ECD计算确定15和16的稠合双环部分的绝对构型。化合物16对小鼠淋巴瘤细胞系L5178 Y（IC 50 8.9 μ M）以及对人卵巢癌细胞系A2780（IC 50 2.7 μ M）显示出中等的细胞毒性，而立体异构体15的活性相当低。
The fungus Penicillium canescens was isolated from the inner tissue of the Mediterranian sponge Agelas oroides. Fermentation of the fungus on solid rice medium yielded one new chlorinated diphenyl ether (1) and 13 known compounds (2-14). Addition of 5% NaBr to the rice medium increased the amounts of 4-6, while lowering the amounts of 8, 12, and 14. Furthermore, it induced the accumulation of 17 and two new brominated azaphilones, bromophilones A and B (15 and 16). Compounds 15 and 16 are the first example of azaphilones with the connection of a benzene moiety and the pyranoquinone core through a methylene group. The structures of the new compounds were elucidated based on the 1D and 2D NMR spectra as well as on HRESIMS data. The absolute configuration of the condensed bicyclic moiety of 15 and 16 was determined by sTDA ECD calculations. Compound 16 exhibited moderate cytotoxicity against the mouse lymphoma cell line L5178Y (IC50 8.9 mu M), as well as against the human ovarian cancer cell line A2780 (IC50 2.7 mu M), whereas the stereoisomer 15 was considerably less active.