Syntheses and biological activities of rebeccamycin analogues with uncommon sugars

    Authors

    G. S. Zhang; J. Shen; H. Cheng; L. Z. Zhu; L. Y. Fang; S. Z. Luo; M. T. Muller; G. E. Lee; L. J. Wei; Y. G. Du; D. X. Sun;P. G. Wang

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    TOPOISOMERASE-I; INDOLOCARBAZOLE GLYCOSIDES; PRACTICAL SYNTHESIS; ANTICANCER AGENT; ANTITUMOR; J-107088; NB-506; FERMENTATION; INHIBITION; SUBSTANCE; Chemistry, Medicinal

    Abstract

    Rebeccamycin analogues containing uncommon sugars and substitutions on the imide nitrogen have been synthesized. Their cytotoxicities were tested in colon cancer and leukemia cells. Their ability to target topoisomerase I was examined using the in vivo complex of the topoisomerase bioassay in Hela cells. Compared with aglycon 1, the modified compounds with various sugar moieties showed more potent cytotoxicities and topo I targeting ability. In addition, the rebeccamycin analogues with various uncommon sugars showed distinct cytotoxicities and topo I targeting activities. The activity of compounds with 2-deoxyglucose (8 and 9) > compounds with 2,6-deoxyglucose (5 and 6) > compounds with 2,3,6-deoxyglucose (10). Furthermore, the anticancer activity of compounds correlated with their ability to target endogenous topo I. These results suggest that the sugar moiety, especially the 2-OH and 6-OH group of the sugar, rather than the modifications in imide structure on the indolocarbazole ring, is a key element for its activity.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    48

    Issue/Number

    7

    Publication Date

    1-1-2005

    Document Type

    Article

    Language

    English

    First Page

    2600

    Last Page

    2611

    WOS Identifier

    WOS:000228111500036

    ISSN

    0022-2623

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