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Telomerase Inhibitors from Cyanobacteria: Isolation and Synthesis of Sulfoquinovosyl Diacylglycerols from Microcystis aeruguinosa PCC 7806

Authors

  • Dr. Malika Makhlouf Brahmi,

    1. Department of Chemistry, University of Basel, National Centre of Competence in Research “Chemical Biology”, 4056 Basel (Switzerland)
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  • Dr. Cyril Portmann,

    1. Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Danilo D'Ambrosio,

    1. Biomolecular Screening Facility, SV-PTECH-PTCB, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Dr. Tom M. Woods,

    1. Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Damiano Banfi,

    1. Biomolecular Screening Facility, SV-PTECH-PTCB, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Patrick Reichenbach,

    1. Lingner Lab, SV-ISREC-UPLIN, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Laeticia Da Silva,

    1. Department of Chemistry, University of Basel, National Centre of Competence in Research “Chemical Biology”, 4056 Basel (Switzerland)
    2. Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Emilie Baudat,

    1. Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Dr. Gerardo Turcatti,

    Corresponding author
    1. Biomolecular Screening Facility, SV-PTECH-PTCB, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
    • Biomolecular Screening Facility, SV-PTECH-PTCB, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Prof. Dr. Joachim Lingner,

    Corresponding author
    1. Lingner Lab, SV-ISREC-UPLIN, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
    • Lingner Lab, SV-ISREC-UPLIN, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
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  • Prof. Dr. Karl Gademann

    Corresponding author
    1. Department of Chemistry, University of Basel, National Centre of Competence in Research “Chemical Biology”, 4056 Basel (Switzerland)
    2. Chemical Synthesis Laboratory, SB-ISIC-LSYNC, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne (Switzerland)
    • Department of Chemistry, University of Basel, National Centre of Competence in Research “Chemical Biology”, 4056 Basel (Switzerland)
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Abstract

By using the Telospot assay, 27 different extracts of cyanobacteria were evaluated for telomerase inhibition. All extracts showed varying, but significant activity. We selected Microcystis aeruguinosa PCC 7806 to identify the active compound and a bioassay guided fractionation led us to isolate mixtures of sulfoquinovosyl diacylglycerols (SQDGs), which were identified by 2D NMR and MS/MS experiments. Pure SQDG derivatives were then synthesized. The IC50 values of pure synthetic sulfoquinovosyl dipalmitoylglycerol and the monopalmitoylated derivative against telomerase were determined to be 17 and 40 μM, respectively. A structure–activity relationship study allowed the identification of compounds with modified lipophilic acyl groups that display improved activity.

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