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High antitumor selectivity of bisimidazoacridones is a function of the aromatic chromophores

  1. Author:
    Cholody, W. M.
    Czerwinski, G.
    Michejda, C. J.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A1484
  4. Type of Work: Meeting Abstract
  1. Abstract:

    We have previously reported that symmetrical bisimidazoacridones (BIA) in which two planar chromophores were joined by a suitable linker possessed high and selective antitumor activity. We also found that even small structural changes in the aromatic ring systems can dramatically modify antitumor selectivity of BIAs. To further investigate the structural requirements for high activity and, especially selectivity in this class of compounds, we synthesized several analogs of BIA in which one imidazoacridone system was replaced with a planar aromatic system such as ellipticine, naphthalimide, acridine and others. The new derivatives were tested in the NCI screen on 60 human tumor cell lines and in clonogenic assays of selected tumors. Preliminary data suggest that the high selectivity observed with BIAs is strictly attributed to the presence of two imidazoacridone (or triazoloacridone) chromophores in the molecule of the drug. However, some of the new compounds showed high, although less selective, antitumor activity, and should be investigated further.

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