Structure-mutagenicity relationships of four amino-imidazonaphthyridines and imidazoquinolines

✍ Scribed by R. Vikse; F. T. Hatch; N. W. Winter; M. G. Knize; S. Grivas; J. S. Felton

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 477 KB
• Volume: 26
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/em.2850260112

✦ Synopsis

We tested four isomeric imidazonaphthyridines and one imidazoquinoline compound for mutagenic activity in the Ames/Salmonella mutagenicity assay, using strain TA98 and strain YG1024, an analogue of strain TA98 with elevated Oocetyltransferase levels. Their potency was related to cal-culated electronic parameters. Five compounds with a linear arrangement of 3 rings showed a positive response in strain YGlO24. Compound 2 (1 -methylimidazo [4,5-b][ 1,7]naphthyridin-2amine) is the most mutagenic in both strains, giving specific activ-ities of about 200 and 30 revertants per microgram in strains YG1024 and TA98, respectively. Three of the compounds were weak mutagens, giving a positive doseresponse only in strain YGl024, with 3-5 revertants per microgram. A higher response of all five compounds in strain YG1024 as opposed to TA98 indicates that they require Oocetyltransferase activity for their metabolism. Mutagenic potencies in strain YG 1024 were positively correlated to the energy of the LUMO (lowest unoccupied molecular orbital) of the nitrenium ion.