Dereplication strategies for targeted isolation of new antitrypanosomal actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49

Usama Ramadan Abdelmohsen, Cheng Cheng, Christina Viegelmann, Tong Zhang, Tanja Grkovic, Safwat Ahmed, Ronald J Quinn, Ute Hentschel, RuAngelie Edrada-Ebel

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78 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)1220-1244
Number of pages25
JournalMarine Drugs
Volume12
Issue number3
DOIs
Publication statusPublished - 6 Mar 2014

Keywords

  • actinosporins
  • spheciospongia vagabunda
  • actinokineospora
  • anti-trypanosomal
  • dereplication
  • secondary metabolomics

Research Output

  • 78 Citations
  • 1 Conference Contribution

Metabolomic strategies in dereplication for targeted cultivation and isolation of new bioactive secondary metabolites from fungal endophytes and marine microbial symbionts

Cheng, C., Abdelmohsen, U. R., Grkovic, T., Quinn, R., Hentschel, U. & Edrada-Ebel, R., Aug 2013, In : Planta Medica. 79, 13, 1 p., SL29.

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