The synthesis and biological activity of 2-substituted malondialdehydes
Date
1983
Authors
Abbott, David Paul
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Abstract
The synthesis of 2-aryl- and 2- methylmalondialdehydes is described, commencing with commercially available substrates. This class of compounds represents the C-conjugation of the electrophilic side chain with a substituent polycyclic aromatic hydrocarbon, both putative mutagens. Although 0-conjugates of polycyclic aromatic hydrocarbons are well documented, and known to be formed in nature, the properties of polar C-conjugates are relatively unexplored. The 2-arylmalondialdehydes, (~hich exist as 8-hydroxy acroleins) and two classes of derivatives, the S-N,N-dimethylaminoacroleins, and the 8-ethoxyacroleins were tested for mutagenicity using the Ames system. A new strain of Salmonella typhimurium, TR2705 (TA94), was used which is more sensitive to cross linking agents such as malondialdehyde. The aromatic substituents investigated were phenyl, 1- and 2-naphthyl, 1-pyrenyl, 6-chrysenyl, and 1-benzo(a)pyrenyl.
None of these proved positive in TR2705, but three benzo(a)pyrene derivatives, the acetamide, the N,N-dimethylaminoacrolein, and the malondialdehyde, were found to be positive in TA98, a strain sensitive to PAR. S-Methoxyacrolein itself was found to be positive in TR2705, while malondialdehyde was less so. Interestingly, even 2-methyl-3-ethoxyacrolein was statistically inactive, showing the deactivating effect of a 2-substituent.
The utility of colorimetric tests for 2-substituted malondialdehydes was also investigated. The commonly used reagent, thiobarbituric acid, which gives a distinct red colour at 532nm with unsubstituted malondialdehyde, does not give a colour with the 2-substituted compounds 2- Methylindole , however, does give a colorimetric test ( A max ~ 560nm). The intensity of the colour was dependent on the point of substitution on the aromatic ring.