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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 52 (1996), S. 75-80 
    ISSN: 1420-9071
    Keywords: Acylfulvene ; illudin S ; sesquiterpene ; antitumor agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Acylfulvene, derived from the sesquiterpene illudin S by treatment with acid (reverse Prins reaction), is far less reactive to thiols than illudin S. However, it is reduced readily to an aromatic product, in the same way as illudin S. This may explain its greatly improved therapeutic index compared to that of the parent compound.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Key words Illudin ; Chemotherapeutic ; Multidrug resistance ; Omphalotus illudens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Illudins are novel low molecular weight natural products cytotoxic to human tumor cells in vitro. Illudin-derived analogs are effective against experimental human cancers nonresponsive to conventional anticancer agents. It is not known why some illudin analogs are more efficacious in vitro and in vivo than other analogs. Therefore, the in vitro cytotoxicity of the parent compound illudin S towards tumor cells was characterized using radiolabeled drug. Two cell lines sensitive at nanomolar concentrations using only a 15-min exposure period displayed a saturable, energydependent accumulation of illudins with relatively low Km and high Vmax values. A nonsensitive cell line, requiring millimolar concentrations to achieve in vitro toxicity, showed minimal illudin uptake with higher Km and lower Vmax values. No release of radioactivity could be demonstrated from tumor cells, indicating that there was no efflux of illudin S (or metabolites) from these cells. The number of intracellular illudin S molecules required to kill 50% of cells of different tumor cell lines varied from 78 000 to 1 114 000 molecules per cell and was correlated with the 2-h IC50 value determined using a colony-forming assay. Illudin S was cytotoxic to a variety of multidrug-resistant tumor cell lines regardless of whether resistance was mediated by gp170/mdrl, gp180/MRP, GSHTR-pi, topoisomerase I,topoisomerase II, increased DNA repair capacity, or alterations in intracellular thiol content. Information obtained in this study could be used to design clinical phase I trials and to develop analogs with improved therapeutic indexes.
    Type of Medium: Electronic Resource
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