Design and synthesis of anthracycline and distamycin derivatives as new, sequence-specific, DNA-binding pharmacological agents

  • Arcamone F
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Abstract

The scope of this work is the improvement of pharmacological properties of DNA-binding antibiotics such as the intercalating antitumor anthracycline aminoglycosides and the minor groove-binding pyrroleamidine oligopeptides specific for A + T-rich sequences. Design of the compounds is based on attempts to increase the affinity of the drugs towards their putative molecular target, either by modification of the electronic environment of relevant atomic groups (fluoroanthracyclines), or by introduction of alkylating functions (distamycin-derived nitrogen mustards). The new pharmacological agents are obtained by total synthesis or semisynthesis and their properties are verified by physicochemical methods and biological testing. © 1994.

Author-supplied keywords

  • Antitumor antibiotics
  • distamycin derivatives
  • fluoroanthracyclines

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Authors

  • Federico Arcamone

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