A comparison of the requirements for antitumour activity and antibacteriophage lambda activity for a series of non-intercalative DNA-binding agents.
A series of non-intercalative DNA-binding agents, comprising mainly bisquaternary ammonium heterocyclic compounds, has been found to inhibit strongly the production of bacteriophage lambda following its induction in Escherichia coli. The inhibition is much greater than that found with a number of DNA intercalating agents, including 9-aminoacridine, ethidium and Daunorubicin. The inhibition correlated significantly with antitumour effect, as measured in a life extension assay with L1210 leukaemia. Activity in both biological systems demanded the presence of strongly charged groups and a rigid co-planar aromatic skeleton, these requirements being almost identical to those needed to displace ethidium efficiently from DNA in a simple assay system. It is suggested that biological activity is associated with the ability of these agents to bind in the minor groove of the DNA double helix. Data on the antibacteriophage action of one of these agents suggests possible models for antitumour activity.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D010582:Bacteriophage lambda / Q000187:drug effects*; D004247:DNA; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007364:Intercalating Agents / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014775:Virus Activation / Q000187:drug effects
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D007364:Intercalating Agents; D000644:Quaternary Ammonium Compounds; D004247:DNA