Quantitative Structure-Toxicity Relationships Using Tops-Mode. 2. Neurotoxicity of a Non-Congeneric Series of Solvents

Abstract

Neurotoxicities of a series of solvents in rats and mice have been modeled by means of the TOPS-MODE approach. Two quantitative structure-toxicity relationship (QSTR) models were obtained explaining more than 80% of the variance in the experimental values of neurotoxicity of 45 solvents. Only one compound was detected as statistical outlier for these models. In contrast, previous models explained less than 60% of the variance in this property for 44 solvents. Finally, the contributions to neurotoxicity in rats and mice for a series of structural fragments were found. Structural characteristics of chlorinated fragments responsible for their different neurotoxicities were analyzed. The differences in neurotoxic behavior of some fragments in rats and mice were also analyzed, which could give insights on the toxicological mechanism of action of solvents studied.

TOPS‐MODE Approach for the Prediction of Blood–Brain Barrier Permeation

“…The TOPS‐MODE approach,23 based on the calculation of the spectral moments of the bond matrix of molecular graph, has been used to generate graph–theoretical descriptors, expressing physical and biological properties in terms of substructural features of molecules. This approach has been successfully applied to different QSPR and QSAR studies 24–30…”

Rational design of new agrochemical fungicides using substructural descriptors

“…The approach including the calculation of the spectral moments of the bond adjacency matrix is known as the TOPS‐MODE (TOPological Substructural MOlecular DEsign) approach, and it has been applied for the description of some physicochemical properties of organic compounds,25, 26 in the quantitative structure–toxicity relationship (QSTR)27–29 and also in the modelling of pharmacological activities 30, 31. The theoretical background for the spectral moments of the bond adjacency matrix has been described in many papers;25–31 however, the present explanation will focus on the most important aspects. In this approach the molecular structure is codified by means of the edge adjacency matrix E (commonly called the bond adjacency matrix B ).…”

How the Parts Organize in the Whole? A Top-Down View of Molecular Descriptors and Properties for QSAR and Drug Design

“…Other works have been devoted to the understanding of skin sensitization mechanisms [42,43], the study of mutagenic activity in dental monomers [44], the prediction of rodent carcinogenicity [45], the prediction of nitrocompounds carcinogeneicity [46] and the study of chromosome aberrations produced by drugs and drug-like compounds [47]. The prediction and understanding of the behaviour of organic chemicals in the environment or human health after the exposition of diverse doses of such compounds has also been studied by using TOPS-MODE [48,49].…”