The structural basis for the mutagenicity of aristolochic acid.
Molecular orbital calculations with aristolochic acid I (AAI) and the model compounds 8-nitro-1-naphthoic acid (1,8NNA) and 3-nitro-2-naphthoic acid (2,3NNA) confirm a similar conformation of the nitro and carboxyl groups in these molecules. The ortho isomer 2,3NNA is not mutagenic in the Salmonella strains TA 100 or TA 1537, but the peri-substituted 1,8NNA shows mutagenic activity similar to AAI in TA 100, although it is only weakly active in TA 1537. We propose a mechanism of activation via a cyclic nitrenium ion with an aristolactam structure which is possible only in peri-substituted nitro carboxylic acids.
Pfau
W
W
German Cancer Research Center, Institute of Toxicology and Chemotherapy, Heidelberg.
Pool-Zobel
B L
BL
von der Lieth
C W
CW
Wiessler
M
M
D034341:Aristolochic Acids; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry* / Q000633:toxicity; D010616:Phenanthrenes / Q000737:chemistry* / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics
D034341:Aristolochic Acids; D009153:Mutagens; D010616:Phenanthrenes; C000228:aristolochic acid I