title: Metabolic Profiling as a Screening Tool for Cytotoxic Compounds: Identification of 3-Alkyl Pyridine Alkaloids from Sponges Collected at a Shallow Water Hydrothermal Vent Site North of Iceland.
abstract: Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified asHaliclona (Rhizoniera) rosea(Bowerbank, 1866). Therefore, these specimens were selected for further investigation.Haliclona roseametabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík 107, Iceland. eydisei@hi.is.
authors.forename: Eydis
authors.initials: E
authors.lastname: Einarsdottir
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavík 101, Iceland. mam5@hi.is.
authors.forename: Manuela
authors.initials: M
authors.lastname: Magnusdottir
authors.affiliation: Denali Therapeutics, South San Francisco, CA 94080, USA. gastarita@gmail.com.|Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA. gastarita@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.affiliation: Helmholtz Center for Polar and Marine Research, Alfred-Wegener-Institute, Bremerhaven D-27570, Germany. mkoeck@awi.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Köck
authors.affiliation: Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. helgaogm@hi.is.
authors.forename: Helga M
authors.initials: HM
authors.lastname: Ögmundsdottir
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík 107, Iceland. margreth@hi.is.
authors.forename: Margret
authors.initials: M
authors.lastname: Thorsteinsdottir
authors.affiliation: Department of Biology and KG Jebsen Centre for Deep Sea Research, University of Bergen, Bergen 5020, Norway. hans.rapp@bio.uib.no.
authors.forename: Hans Tore
authors.initials: HT
authors.lastname: Rapp
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík 107, Iceland. sesselo@hi.is.
authors.forename: Sesselja
authors.initials: S
authors.lastname: Omarsdottir
authors.affiliation: Center for Biomedicine, European Academy of Bolzano/Bozen, Bolzano 39100, Italy. giuseppe.paglia@eurac.edu.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglia
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D047129:Haliclona / Q000737:chemistry / Q000378:metabolism; D060086:Hydrothermal Vents / Q000737:chemistry*; D007055:Iceland; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D011161:Porifera / Q000187:drug effects* / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000470:Alkaloids; D011725:Pyridines; D011726:Pyridinium Compounds; C482411:Viscosamine; C506226:viscosaline; D014867:Water; C023666:pyridine
keywords: Haliclona rosea; ion mobility; marine natural products; metabolomics; sponges