Quantitative Structure‐Toxicity Models for Heterogeneous Aliphatic Compounds

The presented work deals with the Quantitative Structure–Activity Relationships (QSAR) analysis for the growth inhibition of the ciliated protozoan Tetrahymena pyriformis by a mechanistically diverse set of aliphatic organic compounds. A pool of 1509 theoretical descriptors coding for lipophilic, constitutional, steric, and electronic properties of these molecules is calculated with the Dragon software. The simultaneous linear regression analyses on 370 compounds led to a five‐parameter model characterized by R=0.909 and leave more out Rl‐30%‐o=0.843. An external test set of 100 structurally related derivatives that is not employed during the model development demonstrates that the relationship found shows good predictive power, with Rval=0.881. Finally, the application of this subset of descriptors on the complete set of 470 aliphatic structures outperforms previous reported results. Our study corroborates that hydrophobicity, calculated among more than a thousand of structural variables, represents an important factor for predicting the toxicity of aliphatic compounds.