New dimeric analogs of ethidium: synthesis, interaction with DNA, and antitumor activity

Publisher Website
Google Scholar
Abstract
Three new dimeric analogs of ethidium cation in which the monomeric moieties are linked at the 3'' positions by .alpha.,.omega.-diethers of varying length and composition were synthesized. The circular dichroism spectra of all 3 compounds indicate that they double intercalate, and their effects on the thermal helix-coil transition profile of poly(dA-dT) show extremely high affinity for helical DNA, with details of the binding interaction depending on the length and composition of the connecting chain. The ability of the compounds to inhibit nucleic acid synthesis in [mouse leukemia] L1210 cell culture also differed significantly, as did their antitumor effects against P388 leukemia and [mouse] B16 melanoma. The compound with 10 methylene groups in the connecting chain is 5-20 times as potent as eithidium against murine P388 leukemia. These results clearly illustrate the advantage gained by incorporating a weak antitumor agent in a double-interacalating analog.