Apparent changes in structure-activity relationships for antimitochondrial effects of 9-anilinoacridines according to Saccharomyces cerevisiae strain and methodology.
Sensitivity of detection of antimitochondrial effects in S. cerevisiae as measured by the induction of 'petite' mutants, has been investigated in a closely related series of 9-anilinoacridines, using a new microtitre test which has been compared to a range of other techniques. Drugs were chosen to span antimitochondrial activity between the inactive compounds 9-amino- or 3-amino-acridine and the moderately active proflavine, also between proflavine and the strong antimitochondrial agent, ethidium bromide. As previously reported using other techniques, no compound without an amino substituent caused antimitochondrial effects, whereas all 9 anilinoacridines with a 1'-substituted anilino group and 3,6-diamino-substituted acridine ring acted like ethidium in causing strong 'petite' mutagenesis. Compounds with a single acridine 3-amino group, together with proflavine, might or might not be scored as an antimitochondrial agent depending on the time and conditions of drug exposure and, more importantly, on the selection of yeast strain used in the screening. Measurement of 'petite' mutagenesis in strain 5178B, using the microtitre assay, provided the most sensitive and efficient means of detection of antimitochondrial effects for all physical DNA-binding agents. Detailed interpretation of structure-activity relationships and prediction of carcinogenic activity based upon induction of 'petite' mutagenesis would vary considerably if this procedure is not followed.
D000585:Aminacrine / Q000031:analogs & derivatives / Q000633:toxicity*; D000609:Aminoacridines / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship
D000609:Aminoacridines; D009153:Mutagens; D000585:Aminacrine