Antitumor activity of new anthraquinone derivatives

Seven new 9,10-anthracenedione derivatives bearing positively-charged side chains at different positions of the condensed ring system have been investigated in their interaction with DNA and their biological effects, including antitumor activity in the P 388 mouse miniscreen. The drug's affinity for DNA was found to be related to the efficacy of inhibition of cell growth and nucleic acid synthesis for a number of cell lines. Moreover, alkaline elution experiments showed a close relationship between mutagenic potential and cytotoxicity. With the exception of one, all compounds behaved like intercalating agents, as shown by the unwinding of supercoiled plasmid DNA. DNA appeared, therefore, to be the more important target for drug action. The marginal in vivo activity shown by two substances in this series suggests a number of possible structural modifications which may increase their therapeutic efficacy.