Structure-activity relationships for the mutagenic activity of tricyclic intercalating agents in Salmonella typhimurium.

A total of 25 different tricyclic DNA-intercalating chromophores bearing a common -CONH(CH2)2N(CH3)2 solubilizing sidechain have been compared with the 'classical' frameshift mutagen 9-aminoacridine for their ability to induce revertants in Salmonella typhimurium strain TA1537 (sensitive to frameshift mutation by acridine mutagens). The compounds showed varying levels of activity in this strain. For the fused linear and fused angular tricyclics, activity varied from zero to similar levels to 9-aminoacridine, but with no discernable relationship between activity and either structure or the measured physico-chemical properties. However, the '2-1' tricyclic compounds had essentially no mutagenic activity. Since several of these compounds have high in vivo antitumor activity, this is useful knowledge.