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Cellular Localisation of Antitumoral 6-Alkyl Thymoquinones Revealed by an Alkyne–Azide Click Reaction and the Streptavidin–Biotin System

Authors

  • Katharina Effenberger-Neidnicht,

    1. Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth (Germany), Fax: (+49) 921-552671
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  • Dr. Sandra Breyer,

    1. Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth (Germany), Fax: (+49) 921-552671
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  • Katharina Mahal,

    1. Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth (Germany), Fax: (+49) 921-552671
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  • Dr. Randi Diestel,

    1. Helmholtz Centre for Infection Research (HZI), Department of Chemical Biology, Inhoffenstrasse 7, 38124 Braunschweig (Germany)
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  • Dr. Florenz Sasse,

    1. Helmholtz Centre for Infection Research (HZI), Department of Chemical Biology, Inhoffenstrasse 7, 38124 Braunschweig (Germany)
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  • Prof. Rainer Schobert

    Corresponding author
    1. Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth (Germany), Fax: (+49) 921-552671
    • Organic Chemistry Laboratory, University Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth (Germany), Fax: (+49) 921-552671
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Abstract

The subcellular distribution and accumulation of thymoquinone 1, a natural anticancer agent, has hitherto been unknown. We prepared 6-(dec-9-ynyl)thymoquinone 3, an alkyne-labelled derivative with anticancer activity similar to that of its parent compound 1. Alkyne 3 was seen, after a Huisgen-type click reaction with 3-azido-7-hydroxycoumarin, to accumulate in distinct compartments of the nuclei of PtK2 potoroo kidney cells, and in adjoining regions that were stained with an antibody specific for the Golgi apparatus. In contrast, a biotinlabelled thymoquinone 4 seemed to accumulate across the entire cell nucleus upon visualisation with streptavidin; but this was less easily traceable because of co-staining of other structures such as mitochondria. In conclusion, for small drug-like molecules, visualisation by alkyne–azide cycloaddition seems to be superior to conventional visualisation by the biotin–streptavidin system.

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