title: Hycanthone and its congeners as bacterial mutagens.
abstract: Hycanthone methanesulfonate (HCT) was shown to induce "forward" and "reverse" mutations in Salmonella typhimurium and Escherichia coli. Mutational effects of HCT on S. tyhhimurium TA1532 were concentration and time dependent. A comparison of mutagenic potency for TA1532 was made between HCT and the frame-shift mutagens quinacrine and ICR-191. An investigation of structure-activity relationships revealed the substituent in the 4-position of ring A to be critical for mutagenicity. Activity was found when this group was a hydroxymethyl (i.e., HCT) or an aldehyde (Win 25,315), but the analogues having a carboxyl group (Win 25,850) or methyl group (lucanthone) in this positionwere inactive. Removal of a single ethyl group from the side chain did not affect mutagenic activity inasmuch as the potency of desethyl HCT (Win 27,262) equaled that of HCT on a molar basis. A marginal activity was found with a sample of HCT sulfoxide (win 27,266), but this sample was found to contain traces of HCT. The HCT analogue with a terminal N-oxide in the side chain (Win 29,329) was inactive at the concentration tested.
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D006826:Hycanthone / Q000494:pharmacology*; D009153:Mutagens; D011796:Quinacrine / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects; D013892:Thioxanthenes / Q000494:pharmacology*
chemical_list: D004269:DNA, Bacterial; D009153:Mutagens; D013892:Thioxanthenes; D006826:Hycanthone; D011796:Quinacrine