title: Potential antitumor agents. 54. Chromophore requirements for in vivo antitumor activity among the general class of linear tricyclic carboxamides.
abstract: 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.
authors.affiliation: Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
authors.forename: B D
authors.initials: BD
authors.lastname: Palmer
authors.forename: G W
authors.initials: GW
authors.lastname: Rewcastle
authors.forename: G J
authors.initials: GJ
authors.lastname: Atwell
authors.forename: B C
authors.initials: BC
authors.lastname: Baguley
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000585:Aminacrine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000378:metabolism; D004147:Dioxins / Q000138:chemical synthesis / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000473:pathology; D013329:Structure-Activity Relationship; D014439:Tyramine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D004147:Dioxins; D006571:Heterocyclic Compounds; D007364:Intercalating Agents; C055429:ethynyltyramine; D000585:Aminacrine; C023614:dibenzofuran; D004247:DNA; C020887:dibenzo(1,4)dioxin; D014439:Tyramine