Quantitative Structure–Toxicity Relationships Using Tops-Mode. 1. Nitrobenzene Toxicity to Tetrahymena Pyriformis

Abstract The TOPological Sub-Structural MOlecular DEsign (TOPS-MODE) approach (Estrada, E. SAR QSAR Environ. Res. 2000, 11, 55–73) has been introduced to the study of toxicological properties. The toxicity of 42 nitrobenzenes was studied with this approach obtaining a good quantitative structure–toxicity model. For the first time we compare the use of eight different weights in the diagonal entries of the bond matrix for selecting the best TOPS-MODE model. TOPS-MODE was used to derive the contribution of different fragments to the toxicity of studied compounds. These contributions were applied to calculate toxicity substituent constants for the groups present in the nitrobenzenes studied.

[1]  Humberto González Díaz,et al.  Modeling Diamagnetic and Magnetooptic Properties of Organic Compounds with the TOSS-MODE Approach , 2000, J. Chem. Inf. Comput. Sci..

[2]  Lemont B. Kier,et al.  Structure-activity relationship studies on the toxicities of benzene derivatives: II. An analysis of benzene substituent effects on toxicity , 1986 .

[3]  Lemont B. Kier,et al.  Structure—activity relationship studies on the toxicity of benzene derivatives: III. Predictions and extension to new substituents , 1989 .

[4]  J. Dearden,et al.  QSAR in Toxicology. 1. Prediction of Aquatic Toxicity , 1995 .

[5]  Ernesto Estrada,et al.  Spectral Moments of the Edge Adjacency Matrix in Molecular Graphs. 3. Molecules Containing Cycles , 1998, J. Chem. Inf. Comput. Sci..

[6]  D. Roberts.  An Analysis of Published Data on Fish Toxicity of Nitrobenzene and Aniline Derivatives , 1987 .

[7]  A. Balaban,et al.  Vertex- and Edge-Weighted Molecular Graphs and Derived Structural Descriptors , 2000 .

[8]  Ernesto Estrada.  Generalized Spectral Moments of the Iterated Line Graphs Sequence. A Novel Approach to QSPR Studies , 1999, J. Chem. Inf. Comput. Sci..

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

[10]  Ernesto Estrada.  Characterization of 3D molecular structure , 2000 .

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

[12]  E Estrada.  On the Topological Sub-Structural Molecular Design (TOSS-MODE) in QSPR/QSAR and Drug Design Research , 2000, SAR and QSAR in environmental research.

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

[14]  S Ram,et al.  Quantitative structure-activity relationships. , 1979, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

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

[16]  Ernesto Estrada,et al.  Spectral Moments of the Edge-Adjacency Matrix of Molecular Graphs, 2. Molecules Containing Heteroatoms and QSAR Applications , 1997, J. Chem. Inf. Comput. Sci..

[17]  Ernesto Estrada,et al.  Modelling the diamagnetic susceptibility of organic compounds by a sub-structural graph-theoretical approach , 1998 .

[18]  Ernesto Estrada,et al.  Spectral Moments of the Edge Adjacency Matrix in Molecular Graphs, 1. Definition and Applications to the Prediction of Physical Properties of Alkanes , 1996, J. Chem. Inf. Comput. Sci..

[19]  Lemont B. Kier,et al.  Structure‐activity relationship studies on the toxicities of benzene derivatives: I. An additivity model , 1984 .

[20]  Mark T. D. Cronin.  Computer‐aided Prediction of Drug Toxicity in High Throughput Screening , 1998 .

[21]  D W Roberts,et al.  Molecular orbital parameters as predictors of skin sensitization potential of halo- and pseudohalobenzenes acting as SNAr electrophiles. , 1997, Chemical research in toxicology.

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

[23]  E Estrada,et al.  Modeling chromatographic parameters by a novel graph theoretical sub-structural approach. , 1999, Journal of chromatography. A.

[24]  D W Roberts,et al.  Linear free energy relationships for reactions of electrophilic halo- and pseudohalobenzenes, and their application in prediction of skin sensitization potential for SNAr electrophiles. , 1995, Chemical research in toxicology.

[25]  A. Debnath,et al.  Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds. Correlation with molecular orbital energies and hydrophobicity. , 1991, Journal of medicinal chemistry.

[26]  Milon Tichy,et al.  QSAR IN TOXICOLOGY , 1980 .

[27]  M T Cronin,et al.  Quantitative structure-activity relationships as a tool to assess the comparative toxicity of organic chemicals. , 1995, Chemosphere.

[28]  Eric J. Lien,et al.  Physical Factors Contributing to Hydrophobic Constant π , 1986 .

[29]  Corwin Hansch,et al.  Comprehensive medicinal chemistry : the rational design, mechanistic study & therapeutic application of chemical compounds , 1990 .

[30]  Ernesto Estrada,et al.  A Computer-based Approach to Describe the 13C NMR Chemical Shifts of Alkanes by the Generalized Spectral Moments of Iterated Line Graphs , 2000, Comput. Chem..

[31]  C. Hansch.  Quantitative approach to biochemical structure-activity relationships , 1969 .

[32]  Ramón García-Domenech,et al.  Designing sedative/hypnotic compounds from a novel substructural graph-theoretical approach , 1998, Journal of computer-aided molecular design.

[33]  E Estrada,et al.  In silico studies for the rational discovery of anticonvulsant compounds. , 2000, Bioorganic & medicinal chemistry.

[34]  Raimund Mannhold,et al.  The hydrophobic fragmental constant approach forcalculating log P in octanol/water and aliphatic hydrocarbon/water systems , 2000 .

[35]  J Devillers.  New trends in (Q)SAR modeling with topological indices. , 2000, Current opinion in drug discovery & development.

[36]  Mark T. D. Cronin,et al.  QSAR STUDY OF THE TOXICITY OF NITROBENZENES TO TETRAHYMENA PYRIFORMIS , 1995 .

[37]  Ernesto Estrada.  Novel Strategies in the Search of Topological Indices , 2000 .