QSAR study of liver specificity of carcinogenicity of N-nitroso compounds

The quantitative structure–activity relationship (QSAR) of N-nitroso compounds (NOCs) for rat liver was developed by a topological sub-structural molecular-descriptors (TOPS-MODE) approach to predict non-liver-carcinogenic and liver-carcinogenic N-nitroso compounds based on a data set of 108 NOCs. Three descriptors calculated solely from the molecular structures of the compounds were selected by enhanced replacement method (ERM) and were weighted, respectively, with atomic weight, bond dipole moments and Abraham solute descriptor partition between water and aqueous solvent systems to indicate the importance of their roles in liver specificity. A detailed discussion on these three descriptors was carried out, and the contributions of different fragments to rat-liver specificity and the interactions among fragments were analyzed. Such results can offer some useful theoretical references for understanding the chemical structural and biological factors related to the liver-specific biological activity of NOCs.

► The used method can discriminate non-liver-carcinogenic and liver-carcinogenic NOCs. ► The method can study some details about liver specificity of carcinogenicity of NOCs. ► The role of molecular substructures and enzymes in liver specificity was discussed.