title: Dereplication strategies for targeted isolation of new antitrypanosomal actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49.
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.
authors.affiliation: Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg D-97082, Germany. usama.ramadan@uni-wuerzburg.de.
authors.forename: Usama Ramadan
authors.initials: UR
authors.lastname: Abdelmohsen
authors.affiliation: Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg D-97082, Germany. c.cheng@strath.ac.uk.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0NR, UK. christina.viegelmann@strath.ac.uk.
authors.forename: Christina
authors.initials: C
authors.lastname: Viegelmann
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0NR, UK. tong.zhang.101@strath.ac.uk.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia. t.grkovic@griffith.edu.au.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. safwat_aa@yahoo.com.
authors.forename: Safwat
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia. r.quinn@griffith.edu.au.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Department of Botany II, Julius-von-Sachs Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs-Platz 3, Würzburg D-97082, Germany. ute.hentschel@uni-wuerzburg.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Hentschel
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0NR, UK. ruangelie.edrada-ebel@strath.ac.uk.
authors.forename: RuAngelie
authors.initials: R
authors.lastname: Edrada-Ebel
mesh_terms: D000192:Actinomycetales / Q000737:chemistry / Q000378:metabolism*; D000464:Alginates / Q000737:chemistry; D000465:Algorithms; D000818:Animals; D001551:Benz(a)Anthracenes / Q000302:isolation & purification*; D001681:Biological Assay; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D005285:Fermentation; D020723:Glucuronic Acid / Q000737:chemistry; D006027:Glycosides / Q000302:isolation & purification*; D006603:Hexuronic Acids / Q000737:chemistry; D018320:Leishmania major / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055432:Metabolomics; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000382:microbiology*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014344:Trypanocidal Agents / Q000302:isolation & purification*; D014346:Trypanosoma brucei brucei / Q000187:drug effects
chemical_list: D000464:Alginates; D001551:Benz(a)Anthracenes; D003470:Culture Media; D006027:Glycosides; D006603:Hexuronic Acids; D014344:Trypanocidal Agents; C000592880:actinosporin A; D020723:Glucuronic Acid