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 as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes 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.

Marine-Derived Macrocyclic Alkaloids (MDMAs): Chemical and Biological Diversity

“…Hydrolysis of the iminium ion functionality led to a tetracyclic seco skeleton with aldehyde functionality. The skeleton and the aldehyde functionality correspond exactly to the skeleton and aldehyde functional group in ircinal A (121). The condensation of the ircinal-type intermediate with tryptamine and oxidation of the resulting product led to manzarnine B (134) (Figure 18).…”

“…In 2017, cyclostellettamine P (193) with C9 and C11 alkyl chains was detected by ion mobility-mass spectrometry [121] (Figure 15). Cyclostellettamines N (181), R (182), O (183), and Q (184) were reported from Haliclona viscosa [119].…”

“…In 2017, cyclostellettamine P ( 193 ) with C9 and C11 alkyl chains was detected by ion mobility–mass spectrometry [ 121 ] ( Figure 15 ).…”

Identification of Cyanobacterial Strains with Potential for the Treatment of Obesity-Related Co-Morbidities by Bioactivity, Toxicity Evaluation and Metabolite Profiling

“…When applied to the cyanobacterial fractions, this technique allowed selecting the ones with a differentiating factor, representing different metabolites compared to the other samples. PCA, allied to metabolite profiling, has successfully resulted in the identification of several secondary metabolites, such as the 3-Alkyl Pyridine Alkaloids found in the sponge Haliclona rosea [44], or in the isolation of those metabolites, as N-Acyl-Taurine Geodiataurine, isolated from the polar sponge Geodia macandrewi [45]. In our study, the use of metabolite profiling and toxicity evaluation allowed to reduce the list of bioactive fractions to a handful of fractions with promising properties.…”

Marine natural products

“…A new congener of the cyclostellettamine family was proposed based upon ion mobility MS data acquired in the time aligned parallel (TAP) fragmentation mode. 525 NMR data for spongia-16-one, 526,527 dendrillol-1 and -2, 528-530 and aplyroseol-6, 531 have been reassigned using a 800 MHz spectrometer aer inconsistencies between the legacy spectroscopic data for these common spongian diterpenoids was noted. 532…”