Design of site specific DNA damaging agents for generation of multiply damaged sites

We describe the synthesis and DNA damaging activities of hybrid molecules in which a purine (adenine) is linked to an intercalating chromophore (acridine) by a polyamino linker. A DNA damaging agent, phenanthroline or para-nitrobenzamide, is tethered to the acridine moiety at various positions. Our goal is to induce upon activation other lesions in close proximity to the abasic site and therefore create cytotoxic multiply damaged sites.