STRUCTURE-MUTAGENICITY RELATIONSHIPS OF 4 AMINO-IMIDAZONAPHTHYRIDINESAND IMIDAZOQUINOLINES

We tested four isomeric imidazonaphthyridines and one imidazoquinoline compound for mutagenic activity in the Ames/Salmonella mutagenicity a ssay, using strain TA98 and strain YG1024, an analogue of strain TA98 with elevated O-acetyl-transferase levels. Their potency was related t o calculated electronic parameters. Five compounds with a linear arran gement of 3 rings showed a positive response in strain YG1024. Compoun d 2 (1-methyl-imidazo[4,5-b][1,7]naphthyridin-2-amine) is the most mut agenic in both strains, giving specific activities of about 200 and 30 revertants per microgram in strains YG1024 and TA98, respectively. Th ree of the compounds were weak mutagens, giving a positive dose-respon se only in strain YG1024, with 3-5 revertants per microgram. A higher response of all five compounds in strain YG1024 as opposed to TA98 ind icates that they require O-acetyltransferase activity for their metabo lism. Mutagenic potencies in strain YG1024 were positively correlated to the energy of the LUMO (lowest unoccupied molecular orbital) of the nitrenium ion. (C) 1995 Wiley-Liss, Inc.