Potential antitumor agents. 54. Chromophore requirements for in vivo antitumor activity among the general class of linear tricyclic carboxamides.

Structure-antitumor activity relationships are reported for a number of different examples (acridine, phenazine, anthracene, acridone, xanthenone, thioxanthenone, anthraquinone, pyridoquinazoline, dibenzodioxin, thianthrene, phenothiazine, phenoxazine, dibenzofuran, carbazole, and pyridoindole) of the general class of N-[2-(dimethylamino)ethyl] linear tricyclic carboxamides. Only the compounds containing coplanar chromophores intercalated DNA. There is an absolute requirement for an oxygen or aromatic nitrogen (possibly as hydrogen-bond acceptors) peri to the carboxamide, together with a planar ring geometry for biological activity. In addition to further delineating the nature of the pharmacophore for this class of compounds, the work has also identified dibenzo[1,4]dioxin as a novel DNA-intercalating chromophore with in vivo antitumor activity.