Mutagenicity of dimethyl heteroaromatic triazenes in the Ames test: the role of hydrophobicity and electronic effects

AJ Shusterman, AK Debnath, C Hansch, GW Horn, FR Fronczek, AC Greene and SF Watkins

Department of Chemistry, Pomona College, Claremont, California 91711.

The mutagenicities of five heterocyclic 3,3-dimethyltriazenes have been evaluated in the Ames test. The octanol-water partition coefficients (P) for these triazenes have been measured, and their electron distributions and molecular orbital energies were calculated using the MNDO semiempirical molecular orbital method. Molecular structures of three triazenes have been determined using X-ray crystallography. The mutagenicities of these five triazenes, which range from nearly inactive to very highly mutagenic, are well predicted by quantitative structure-activity relationships that had been derived previously for the mutagenicity of aryltriazenes. The form of these equations indicates that more hydrophobic and more electron-rich triazenes are more active in the Ames test. This supports the hypothesis that the ease of initial triazene activation by cytochrome P-450 governs the mutagenicity of these compounds.

Volume 36, Issue 6, pp. 939-944, 12/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics