R. Vikse et al., STRUCTURE-MUTAGENICITY RELATIONSHIPS OF 4 AMINO-IMIDAZONAPHTHYRIDINESAND IMIDAZOQUINOLINES, Environmental and molecular mutagenesis, 26(1), 1995, pp. 79-85
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.