title: Cellular localisation of antitumoral 6-alkyl thymoquinones revealed by an alkyne-azide click reaction and the streptavidin-biotin system.
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 PtK(2) 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.
authors.affiliation: Organic Chemistry Laboratory, University Bayreuth, Bayreuth, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Effenberger-Neidnicht
authors.forename: Sandra
authors.initials: S
authors.lastname: Breyer
authors.forename: Katharina
authors.initials: K
authors.lastname: Mahal
authors.forename: Randi
authors.initials: R
authors.lastname: Diestel
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.forename: Rainer
authors.initials: R
authors.lastname: Schobert
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001386:Azides / Q000737:chemistry*; D016227:Benzoquinones / Q000737:chemistry* / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry; D002451:Cell Compartmentation / Q000187:drug effects; D045744:Cell Line, Tumor; D057930:Click Chemistry; D005260:Female; D005453:Fluorescence; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism*; D013194:Staining and Labeling; D019809:Streptavidin / Q000737:chemistry
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D001386:Azides; D016227:Benzoquinones; D001710:Biotin; D019809:Streptavidin; C003466:thymoquinone