Dibenzoylhydrazines as Insect Growth Modulators: Topology-Based QSAR Modelling

Dibenzoylhydrazines Xa-(C6H5)a-CO-N-(t-Bu)-NH-CO-(C6H5)b-Yb are efficient insect growth regulators with high activity and selectivity toward lepidopteran and coleopteran pests. For 123 congeneric molecules, a quantitative structure activity relationship model was built in the framework of the QSARINS package using 2D, Topology-based, PaDEL descriptors. Variable selection by GA-MLR allows building an efficient multilinear regression linking pEC50 values to nine structural variables. Robustness and quality of the model were carefully examined at various levels: data-fitting (recall), leave-one (or some) - out, internal and external validation (including random splitting), points not in depth investigated in previous works. Various Machine Learning approaches (Partial Least Squares Regression, Projection Pursuit Regression, Linear Support Vector Machine or Three Layer Perceptron Artificial Neural Network) confirm the validity of the analysis, giving highly consistent results of comparable quality, with only a slight advantage for the three-layer perceptron

Linear and non-linear modelling of the cytotoxicity of TiO2 and ZnO nanoparticles by empirical descriptors

Titanium oxide (TiO2) and zinc oxide (ZnO) nanoparticles are among the most widely used in different applications in daily life. In this study, local regression and classification models were developed for a set of ZnO and TiO2 nanoparticles tested at different concentrations for their ability to disrupt the lipid membrane in cells. Different regression techniques were applied and compared by checking the robustness of the models and their external predictive ability. Additionally, a simple classification model was developed, which predicts the potential for disruption of the studied nanoparticles with good accuracy (overall accuracy, specificity, and sensitivity >80%) on the basis of two empirical descriptors. The present study demonstrates that empirical descriptors, such as experimentally determined size and tested concentrations, are relevant to modelling the activity of nanoparticles. This information may be useful to screen the potential for harmful effect of nanoparticles in different experimental conditions and to optimize the design of toxicological tests. Results from the present study are useful to support and refine the future application of in silico tools to nanoparticles, for research and regulatory purposes

Structure–activity relationship study of trifluoromethylketone inhibitors of insect juvenile hormone esterase: Comparison of several classification methods

<div><p>Juvenile hormone esterase (JHE) plays a key role in the development and metamorphosis of holometabolous insects. Its inhibitors could possibly be targeted for insect control. Conversely, JHE may also be involved in endocrine disruption by xenobiotics, resulting in detrimental effects in beneficial insects. There is therefore a need to know the structural characteristics of the molecules able to monitor JHE activity, and to develop SAR and QSAR studies to estimate their effectiveness. For a large diverse population of 181 trifluoromethylketones (TFKs) – the most potent JHE inhibitors known to date – we recently proposed a binary classification (active/inactive) using a support vector machine and Codessa structural descriptors. We have now examined, using the same data set and with the same descriptors, the applicability and performance of five other machine learning approaches. These have been shown able to handle high dimensional data (with descriptors possibly irrelevant or redundant) and to cope with complex mechanisms, but without delivering explicit directly exploitable models. Splitting the data into five batches (training set 80%, test set 20%) and carrying out leave-one-out cross-validation, led to good results of comparable performance, consistent with our previous support vector classifier (SVC) results. Accuracy was greater than 0.80 for all approaches. A reduced set of 15 descriptors common to all the investigated approaches showed good predictive ability (confirmed using a three-layer perceptron) and gives some clues regarding a mechanistic interpretation.</p></div

Investigation of the influence of protein corona composition on gold nanoparticle bioactivity using machine learning approaches

The understanding of the mechanisms and interactions that occur when nanomaterials enter biological systems is important to improve their future use. The adsorption of proteins from biological fluids in a physiological environment to form a corona on the surface of nanoparticles represents a key step that influences nanoparticle behaviour. In this study, the quantitative description of the composition of the protein corona was used to study the effect on cell association induced by 84 surface-modified gold nanoparticles of different sizes. Quantitative relationships between the protein corona and the activity of the gold nanoparticles were modelled by using several machine learning-based linear and non-linear approaches. Models based on a selection of only six serum proteins had robust and predictive results. The Projection Pursuit Regression method had the best performances (r2 = 0.91; Q2loo = 0.81; r2ext = 0.79). The present study confirmed the utility of protein corona composition to predict the bioactivity of gold nanoparticles and identified the main proteins that act as promoters or inhibitors of cell association. In addition, the comparison of several techniques showed which strategies offer the best results in prediction and could be used to support new toxicological studies on gold-based nanomaterials

Computational approaches for the prediction of the selective uptake of magnetofluorescent nanoparticles into human cells

The use of functionalized nanomaterials is of high importance in biomedical applications like the efficient targeting of cancer cells. This paper proposes a comparison of different statistical and mechanistic aspects of new QSAR models generated to predict the selective uptake of a library of surface modified nanoparticles tested in different human cell types. Additionally, a new approach based on the combination of multivariate factorial analysis and QSAR is proposed to generate a 2-dimensional map of the selective uptake of the surface modified nanoparticles into multiple cell types. This map offers an immediate view of the uptake of the nanoparticles, distinguishing among those with high or low uptake in one or more of the studied cells. Finally, QSAR models are generated to predict the coordinates of the studied nanoparticles in the 2D map from their molecular structure. This predictive map is useful to screen new and existing surface modified nanoparticles for diagnostic and biomedical uses

Évolution des effets α-fonctionnels en RMN

Les déplacements induits en RMN13C par substitution a fonctionnelle [math] varient très largement en fonction de l'environnement carboné tant en série aliphatique qu'en série alicyclique. Pour prévoir les effets observés sur les composés cycliques nous comparons les comportements d'environnements aliphatiques et alicyliques figés non-contraints. L'analyse factorielle effectuée sur 196 déplacements induits montre qu'environnements aliphatiques et alicycliques se regroupent selon leur connectivité et que le comportement des structures alicycliques peut être décrit par un environnement topographiquement actif (sites α et ß gauches) plutôt que par le squelette aliphatique carboné correspondant ou squelette isotopologue. Par exploitation des corrélations DARC-PULFO établies pour des séries de composés aliphatiques, des paramètres topologiques moyens relatifs à des environnements cycliques [math] sont évalués. Ils rendent compte des effets d'atténuation et d’inversion des déplacements induits dans de nombreuses familles chimiques