Predicting genotoxicity of aromatic and heteroaromatic amines using electrotopological state indices

Abstract

A quantitative structure–activity relationship (QSAR) model relating electrotopological state (E-state) indices and mutagenic potency was previously described by Cash [Mutat. Res. 491 (2001) 31–37] using a data set of 95 aromatic amines published by Debnath et al. [Environ. Mol. Mutagen. 19 (1992) 37–52]. Mutagenic potency was expressed as the number of Salmonella typhimurium TA98 revertants per nmol (LogR). Earlier work on the development of QSARs for the prediction of genotoxicity indicated that numerous methods could be effectively employed to model the same aromatic amines data set, namely, Debnath et al.; Maran et al. [Quant. Struct.-Act. Relat. 18 (1999) 3–10]; Basak et al. [J. Chem. Inf. Comput. Sci. 41 (2001) 671–678]; Gramatica et al. [SAR QSAR Environ. Res. 14 (2003) 237–250]. However, results obtained from external validations of those models revealed that the effective predictivity of the QSARs was well below the potential indicated by internal validation statistics (Debnath et al., Gramatica et al.). The purpose of the current research is to externally validate the model published by Cash using a data set of 29 aromatic amines reported by Glende et al. [Mutat. Res. 498 (2001) 19–37; Mutat. Res. 515 (2002) 15–38] and to further explore the potential utility of using E-state sums for the prediction of mutagenic potency of aromatic amines.