3D-MEDNEs:  An Alternative “In Silico” Technique for Chemical Research in Toxicology. 1. Prediction of Chemically Induced Agranulocytosis

Abstract

A novel approach to molecular negentropy from the point of view of Markov models is introduced. Stochastic negentropies (MEDNEs) are used to develop a linear discriminant analysis. The discriminant analysis produced a set of two discriminant functions, which gave rise to a very good separation of 93.38% of 151 chemicals (training series) into two groups. The total predictability (86.67%, i.e., 52 compounds out of 60) was tested by means of an external validation set. Randić's orthogonalization procedures allowed interpretation of the model while avoiding collinearity descriptors. On the other hand, factor analysis was used to suggest the relation of MEDNEs with other molecular descriptors and properties into a property space. Three principal factors (related to three orthogonal MEDNEs) can be used to explain approximately 90% of the variance of different molecular parameters of halobenzenes including bulk, energetic, dipolar, molecular surface-related, and hydrophobic parameters. Finally, preliminary experimental results coincide with a theoretical prediction when agranulocytosis induction by G-1, a novel microcidal that presents Z/E isomerism, is not detected.

Immunotoxicology: challenges in the 21st century and in vitro opportunities

“…there is no evidence for environmental chemicals playing a major role, though case reports can be found (Knutsen, 1978). they did not warrant test development in vivo or in vitro, but a QSAR has been developed to predict such effects (Díaz et al, 2003).…”

Application of linear discriminant analysis in the virtual screening of antichagasic drugs through trypanothione reductase inhibition

“…The aim of LDA is to find an algorithm capable of distinguishing among two or more categories of objects [29], in this particular case compounds active and inactive against Trypanosoma cruzi through TR inhibition. The use of LDA has been applied extensively in drug discovery, mainly by the Las Villas and the Valencia groups [30][31][32][33][34]. Recently, Meneses-Marcel et al successfully employed this approach in the search of treatment for trichonomiasis, another important parasite-originated disease [35].…”