Quantum Chemical Evaluation and QSAR Modeling of <i>N</i>-Nitrosamine Carcinogenicity

<i>N</i>-Nitrosamine compounds in pharmaceuticals are a major concern due to their carcinogenic potential. However, not all nitrosamines are strong carcinogens, and understanding the structure-activity relationships of this compound group is a major challenge. The determination of the acceptable intake limits for this compound group is determined by applying either a simple carcinogenic potency categorization approach (CPCA) or read-across analysis from simple nitrosamines where experimental data exist. However, the emergence of structurally complex nitrosamines makes quantitative models desirable. Here, we present a two-step modeling approach based on a linear discriminant analysis of a set of quantum mechanical and classical descriptors followed by a 3D-QSAR PLS regression model to predict the logTD₅₀ of nitrosamine compounds.