A novel approach to predict a toxicological property of aromatic compounds in the Tetrahymena pyriformis.

The TOPological Substructural MOlecular DEsign (TOPS-MODE) has been successfully used in order to explain the toxicity in the Tetrahymena pyriformis on a large data set. The obtained models for the training set had good statistical parameters (R(2)=0.72-0.81, p<0.05) an also the prediction power of the models found was adequate (Q(2)=0.70-0.80). A detailed study of the influence of variable numbers in the equation and the statistical outliers was carried out; leading to a good final model with a better physicochemical interpretation than the rest of the published models. Only two molecular descriptors codifying dipolar and hydrophobic features were introduced. Finally, the fragment contributions to the toxicity prediction evidenced the powerful of this topological approach.

[1]  T M Martin,et al.  Prediction of the acute toxicity (96-h LC50) of organic compounds to the fathead minnow (Pimephales promelas) using a group contribution method. , 2001, Chemical research in toxicology.

[2]  T W Schultz,et al.  Quantitative structure-activity analyses of nitrobenzene toxicity to Tetrahymena pyriformis. , 1998, Chemical research in toxicology.

[3]  T W Schultz,et al.  Development of quantitative structure-activity relationships for the toxicity of aromatic compounds to Tetrahymena pyriformis: comparative assessment of the methodologies. , 2001, Chemical research in toxicology.

[4]  Ş. Niculescu,et al.  Using probabilistic neural networks to model the toxicity of chemicals to the fathead minnow (Pimephales promelas): a study based on 865 compounds. , 1999, Chemosphere.

[5]  Mark T. D. Cronin,et al.  QSAR in Toxicology. 3. Prediction of Chronic Toxicities , 1995 .

[6]  N. Draper,et al.  Applied Regression Analysis , 1966 .

[7]  Ernesto Estrada,et al.  A novel approach for the virtual screening and rational design of anticancer compounds. , 2000, Journal of medicinal chemistry.

[8]  Mark T. D. Cronin,et al.  QSAR in Toxicology. 2. Prediction of Acute Mammalian Toxicity and Interspecies Correlations , 1995 .

[9]  Roberto Todeschini,et al.  Handbook of Molecular Descriptors , 2002 .

[10]  T W Schultz,et al.  Structure-Toxicity Analyses of Tetrahymena Pyriformis Exposed to Pyridines - An Examination Into Extension of Surface-Response Domains , 2001, SAR and QSAR in environmental research.

[11]  Mark T. D. Cronin,et al.  QSAR in Toxicology. 4. Prediction of Non‐lethal Mammalian Toxicological Endpoints, and Expert Systems for Toxicity Prediction , 1995 .

[12]  T W Schultz,et al.  Parametrization of electrophilicity for the prediction of the toxicity of aromatic compounds. , 2001, Chemical research in toxicology.