The structural basis for the mutagenicity of aristolochic acid

W Pfau, BL Pool-Zobel, CW von der Lieth, M Wiessler - Cancer letters, 1990 - Elsevier
W Pfau, BL Pool-Zobel, CW von der Lieth, M Wiessler
Cancer letters, 1990Elsevier
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 …
Abstract
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.
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