Potential antitumor agents. 53. Synthesis, DNA binding properties, and biological activity of perimidines designed as minimal DNA-intercalating agents

Abstract
A series of compounds based on perimidine have been synthesized and evaluated for their DNA-binding properties and antitumor activity. The fused tricyclic perimidine chromophore appears to be the minimal structural requirement for intercalative binding to DNA since the mode of binding could be dictated by the position of attachment of the side chain. The intercalating compounds have DNA association constants (log K = 5.8-6.5) and cytotoxic potencies (IC50=500-1500 nM) comparable to those shown by other classes of linear, tricyclic DNA-intercalating antitumor agents (acridinecarboxamides, phenazinecarboxamides), but none of the compounds showed in vivo activity.