Dereplication strategies for targeted isolation of new antitrypanosomal actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49.
Dereplication strategies for targeted isolation of new antitrypanosomal actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49.
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DOI：
10.3390/md12031220
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发表时间：
2014-03-06
期刊：
影响因子：
5.4
通讯作者：
Edrada-Ebel R
中科院分区：
文献类型：
--
作者：
Abdelmohsen UR;Cheng C;Viegelmann C;Zhang T;Grkovic T;Ahmed S;Quinn RJ;Hentschel U;Edrada-Ebel R
采用高分辨率傅里叶变换质谱（HRFTMS）和核磁共振（NMR）光谱作为补充代谢组学工具，以复制新的抗锥虫活性海绵相关细菌Actinokrispora sp. EG 49提取物的化学特征。主成分分析（PCA），层次聚类分析（HCA），正交偏最小二乘判别分析（OPLS-DA）被用来评估从四种不同的发酵方法的粗提物的高分辨力傅立叶变换质谱和核磁共振数据。统计分析确定了最佳的培养条件和提取程序，用于分离新的生物活性代谢产物。结果，从红海海绵Spheciospongia vagabunda培养的放线菌属菌株EG 49的肉汤培养物中分离到两种新的O-糖基化angucyclines，命名为放线菌素A（1）和B（2）。放线菌素A和B的结构通过1D-和2D-NMR技术以及高分辨率串联质谱确定。抗寄生虫特性的测试显示放线菌素A对布氏锥虫具有活性，IC 50值为15 µM;但是没有检测到对利什曼原虫和恶性疟原虫的活性，因此表明其对寄生虫布氏锥虫（昏睡病的病原体）的选择性。
High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC50 value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.
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影响因子：
14.8
作者：
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影响因子：
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