Nitro-aromatic compounds mutagenic activity

In what follows, no explicit attention is given to the specific type of assays or tester strains used to determine the mutagenic activity in nitro-aromatic compounds. This particular choice is made consciously, as the emphasis of this work is on the structural and electronic factors that modulate the mutagenic activity of the nitro-aromatic compounds in general. The interested readers are recommended to refer to the original works for more detailed discussions. 

The position of the nitro group is also an important structural factor in determining the biological activity in nitro-aromatic compounds. This is evident from studies that show markedly different mutagenic potency in structural isomers of nitro-aromatic compounds [3,15, 24, 26, 30, 31,44,46]. Structural isomers like 1-, 2-, 3-, and 6-nitrobenzo[a]pyrene have dramatically different mutagenic potency [47—49] 6-nitrobenzo[a]pyrene is a weak mutagen, while 1-, 2-, and 3-nitrobenzo [a]pyrene are potent mutagenes [47 -9]. 

A QSAR model was developed to test the mutagenicity of 117 nitro-aromatic compounds in bacterial strain cells without metabolic activation [74]. It was shown that hydrophobicity plays a crucial role in determining the relative mutagenicity of most of the compounds studied. The mutagenicity of the nitro-aromatic compounds increases slowly at low logR and then decreases rapidly at high log P. It was suggested that a combination of adverse hydrophobic and steric effects could explain these observations. In a subsequent analysis, Debnath and Hansch [75]... 

The mutagenic activity (rev/yg) by linear regression analysis for the engine emission extracts and selected nitro-aromatic compounds is given in Table 2. Note that the commercially available 1-nitropyrene appears to be contaminated with di-nitropyrenes. 

Since the calculated contribution to mutagenic activity from identified nitro-aromatics is well below 100 percent, several conclusions should be considered (1) nitro-aromatics whose activities are unknown to date contribute significantly to the direct acting activity, (2) compounds other than nitro-aromatics, present in the extracts, are potent mutagens, or (3) nitro-aromatics originally present in the extract oxidized or decomposed with time. 

Debnath, A.K., Hansch, C. (1992) Structure-activity relationship of genotoxic polycyclic aromatic nitro compounds. Further evidence for the importance of hydrophobicity and molecular orbital energies in genetic toxicity. Environ. Mol. Mutagen. 20, 140-144. 

A.K. Debnath et al., Quantitative structure-activity relationship investigation of the role of hydrophobicity in regulating mutagenicity in the Ames test 2 Mutagenicity of aromatic and heteroaromatic nitro compounds in Salmonella typhimurium TA100. Environ. Mol. Mutagen. 19, 53-70 (1992)... 

A.K. Debnath et al., Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds. Correlation with molecular orbital energies and hydrophobicity. J. Med. Chem. 34, 786-797 (1991)... 

Debnath, A.K., Compadre, R.L.L., Debnath, G., Shusterman, A.J. and Hansch, C. (1991). Structure-Activity Relationship of Mutagenic Aromatic and Heteroaromatic Nitro Compounds. Correlation with Molecular Qrbital Energies and Hydrophobicity. J.Med.Chem.,34, 787-797. 

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