Synthesis and biological evaluation of polyamine DNA-intercalator conjugates

One of the major shortcomings of current cancer therapies is the non­selective delivery of the antineoplastic drug to both targeted tumor cells and healthy cells. Enhanced targeting of such drugs could diminish their associated toxicity by reducing their uptake by healthy cells. The strategy delineated in this thesis outlines a new vectoring technology which should direct drugs into specific cell types. Four conjugates (1-4) were synthesized which tether a DNA intercalator (e.g., an acridine or anthracene ring system) to a naturally occurring polyamine (spermidine). The ability of these conjugates to bind to DNA in vitro and to disrupt the proper functioning of topoisomerase II, an enzyme involved in DNA replication was evaluated. These preliminary studies may lead to a new class of vectored chemotherapeutics.