title: 'Petite' mutagenesis in Saccharomyces cerevisiae by a series of 2,7-di-alkyl-substituted derivatives of proflavine with differing DNA-binding properties.
abstract: The ability of proflavine (3,6-diaminoacridine) and its 2,7-dimethyl, 2,7-diethyl, 2,7-diisopropyl and 2,7-di-tert.-butyl derivatives to induce the 'petite' mutation in Saccharomyces cerevisiae has been studied in relation to the DNA-binding properties of the compounds. The nature of the binding has been investigated by nuclear magnetic resonance techniques, and the results support and clarify earlier suggestions that the first 3 members of the series intercalate into DNA while the diisopropyl and di-tert.-butyl compounds do not. Toxicity of the drugs was primarily associated with their mode of DNA binding, but lipophilicity had an important secondary effect. It seems likely that the toxic properties of the more lipophilic DNA-intercalating members of the series mask their potential for 'petite' mutagenesis.
mesh_terms: D000166:Acridines / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D004271:DNA, Fungal / Q000187:drug effects / Q000378:metabolism*; D007364:Intercalating Agents; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens; D009154:Mutation; D011370:Proflavine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D000166:Acridines; D004271:DNA, Fungal; D007364:Intercalating Agents; D009153:Mutagens; D011370:Proflavine