Docking and QSAR comparative studies of polycyclic aromatic hydrocarbons and other procarcinogen interactions with cytochromes P450 1A1 and 1B1.

To obtain chemical clues on the process of bioactivation by cytochromes P450 1A1 and 1B1, some QSAR studies were carried out based on cellular experiments of the metabolic activation of polycyclic aromatic hydrocarbons and heterocyclic aromatic compounds by those enzymes. Firstly, the 3D structures of cytochromes 1A1 and 1B1 were built using homology modelling with a cytochrome 1A2 template. Using these structures, 32 ligands including heterocyclic aromatic compounds, polycyclic aromatic hydrocarbons and corresponding diols, were docked with LigandFit and CDOCKER algorithms.

Polyphosphorylated triphenylenes: synthesis, crystal structure, and selective catechol recognition.

Designed as a multivalent hydrogen bond acceptor, new receptors, Discopus 1a,b, were built from a triphenylene core surrounded by six (diaryl)phosphinate groups. An efficient synthesis was developed to prepare these elaborated structures in a high overall yield. The X-ray structure of receptor 1b showed strong cooperative hydrogen bonds with two water molecules and intermolecular CH-pi contacts.

Homology modelling of the Apis mellifera nicotinic acetylcholine receptor (nAChR) and docking of imidacloprid and fipronil insecticides and their metabolites.

Five homology models for honeybee (Apis mellifera) nicotinic acetylcholine receptor (nAChR) alpha1/beta1, alpha3/beta2, alpha4/beta2, alpha6/beta2 and alpha9/alpha9 subtypes were built from the Torpedo marmorata nAChR X-ray structure. Then, imidacloprid, fipronil and their metabolites were docked into the ligand binding domain (LBD) of these receptors and the corresponding scoring functions were calculated. The binding modes of the docked compounds were carefully analysed.

Decision trees versus support vector machine for classification of androgen receptor ligands.

With the current concern of limiting experimental assays, increased interest now focuses on in silico models able to predict toxicity of chemicals. Endocrine disruptors cover a large number of environmental and industrial chemicals which may affect the functions of natural hormones in humans and wildlife. Structure-activity models are now increasingly used for predicting the endocrine disruption potential of chemicals.

Endocrine disruption profile analysis of 11,416 chemicals from chemometrical tools.

A number of chemicals released into the environment have the potential to disturb the normal functioning of the endocrine system. These chemicals termed endocrine disruptors (EDs) act by mimicking or antagonizing the normal functions of natural hormones and may pose serious threats to the reproductive capability and development of living species. Batteries of laboratory bioassays exist for detecting these chemicals.