Intercalators as anticancer drugs

Intercalators are the most important group of compounds that interact rever sibly with the DNA double helix. Some of them are valuable drugs currently used for the treatment of ovarian and breast cancers and acute leukemias, w hile many others are in different phases of clinical trials. Intercalating agents share common structural features such as the presence of planar polyaromatic systems which bind by insertion between DNA base-pai rs, with a marked preference for 5'-pyrimidine-purine-3' steps. The chromop hores are linked to basic chains that might also play an important role in the affinity and selectivity shown by these compounds. Bisintercalators hav e two potential intercalating ring systems connected by linkers which can v ary in length and rigidity. Nowadays it is well accepted that the antitumor activity of intercalators i s closely related to the ability of these compounds to stabilize the DNA- i ntercalator-topoisomerase II ternary complex. In this work we have carried out a revision of small organic molecules that bind to the DNA molecule via intercalation, and exert their antitumor activity through a proven topoiso merase II inhibition. We have tried to give a general overview of the most recent results in this area, paying special attention to compounds that arc currently under clinical trials. Among those are naphthalimides, a group o f compounds that has been developed in our laboratory since the 70's.