Structure–activity relationships for the mutagenicity and carcinogenicity of simple and α‐β unsaturated aldehydes

Abstract

Aldehydes are important industrial compounds that are used for the synthesis of chemicals and pharmaceuticals and as solvents, food additives, and disinfectants. Because of their reactivity, aldehydes are able to interact with electron-rich biological macromolecules and adverse health effects have been reported, including general toxicity, allergenic reactions, mutagenicity, and carcinogenicity. The cost, time, and number of animals necessary to adequately screen these chemicals places serious limitations on the number of aldehydes whose health potential can be studied and points to the need of using alternative methods for assessing, at least in a preliminary way, the risks associated with the use of aldehydes. A method of choice is the study of quantitative structure-activity relationships (QSARs). In the present work, we present QSAR models for the mutagenicity and carcinogenicity of simple aldehydes and alpha-beta unsaturated aldehydes. The models point to the role of electrophilicity, bulkiness, and hydrophobicity in the genotoxic activity of the aldehydes and lend themselves to the prediction of the activity of other untested chemicals of the same class.

Simple and α,β-unsaturated aldehydes: Correct prediction of genotoxic activity through structure-activity relationship models

“…Table I presents the results of Salmonella reversion assays performed on simple and a,b-unsaturated aldehydes as part of this study, while Tables II and III summarize this data, together with literature data on the compounds used in our previous paper to generate the QSAR models. The literature sources are detailed in our previous paper [Benigni et al, 2003]. Table IV reports SOS Chromotest data collected from the literature.…”

“…In this paper, we considered only the chemical descriptors that were actually entered (used) in the QSAR models derived in our previous paper [Benigni et al, 2003]. Hydrophobicity was parameterized by the logarithm of the octanol/water partition coefficient (log P).…”

“…Toxicological experimentation follows priorities (e.g., level of human exposure) different from those of QSAR modelers. The data on aldehydes we collected from the literature were far from ideal; in spite of this, the QSAR models obtained in our previous paper were formally (statistically) successful, and were scientifically sound [Benigni et al, 2003].…”

“…In a previous paper, we presented quantitative structure-activity relationship (QSAR) models for the genotoxic activity of aldehydes [Benigni et al, 2003]. In that study, we collected literature data on the carcinogenicity and Salmonella typhimurium mutagenicity of the two groups of aldehydes (simple and a,b-unsaturated).…”

Experimental and modelling studies on antifungal compounds

“…QSAR studies carried out on antifungal activity of substituted thiazolidines lead to the conclusions that steric and electronic properties are the essential parameters [8]. QSAR models for the mutagenicity and carcinogenicity of simple aldehydes and unsaturated aldehydes pointed to the role of electrophilicity, bulkiness, and hydrophobicity as the important parameters [20]. Jurs-DPSA-2 (Total Charge Weighted Surface Areas) and Jurs-WPSA-3 (Surface Weighted Charged Partial Surface Areas) are descriptors that characterize molecules through the area of solvent accessible surface (SAS) and partial atomic charges.…”