Azido analogs of acridine: photoaffinity probes for frameshift mutagenesis in Salmonella typhimurium.
In order to identify a photoaffinity probe for 9-aminoacridine frameshift mutagenesis, 20 azido analogs of acridine were synthesized and tested in Ames' Salmonella tester strains, TA1535, TA1537, TA1538 and their corresponding excision-repair-coefficient strains TA1975, TA1977 and TA1978, to determine their mutagenicity and toxicity relative to 9-aminoacridine. The substituent-mutagenicity patterns observed for these compounds agree very well with those obtained previously for non-azidoacridines. The results presented here show that the 2-azido-analog of 9-aminoacridine demonstrates biological activity similar to 9-aminoacridine prior to photolytic activation. With light activation, however, the 9-amino-2-azido derivative becomes more effective at producing frameshift mutations characteristic of 9-aminoacridine. Furthermore, this photolytic enhancement of mutagenesis appears to be due to the repairable lesion suggesting that covalent attachment of the drug occurs.
D000166:Acridines / Q000494:pharmacology*; D000585:Aminacrine / Q000494:pharmacology*; D000609:Aminoacridines / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000235:genetics
D000166:Acridines; D000609:Aminoacridines; D001386:Azides; D009153:Mutagens; D000585:Aminacrine