PUBLICATION
A Computational Approach to Evaluate the Androgenic Affinity of Iprodione, Procymidone, Vinclozolin and Their Metabolites
- Authors
- Galli, C.L., Sensi, C., Fumagalli, A., Parravicini, C., Marinovich, M., Eberini, I.
- ID
- ZDB-PUB-140812-3
- Date
- 2014
- Source
- PLoS One 9: e104822 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Oxazoles/metabolism*
- Species Specificity
- Bridged Bicyclo Compounds/metabolism*
- Molecular Sequence Data
- Humans
- Animals
- Amino Acid Sequence
- Hydantoins/metabolism*
- Protein Structure, Tertiary
- Aminoimidazole Carboxamide/analogs & derivatives*
- Aminoimidazole Carboxamide/metabolism
- Protein Binding
- Zebrafish
- Receptors, Androgen/chemistry
- Receptors, Androgen/metabolism*
- Molecular Docking Simulation*
- Molecular Dynamics Simulation*
- Rats
- PubMed
- 25111804 Full text @ PLoS One
Citation
Galli, C.L., Sensi, C., Fumagalli, A., Parravicini, C., Marinovich, M., Eberini, I. (2014) A Computational Approach to Evaluate the Androgenic Affinity of Iprodione, Procymidone, Vinclozolin and Their Metabolites. PLoS One. 9:e104822.
Abstract
Our research is aimed at devising and assessing a computational approach to evaluate the affinity of endocrine active substances (EASs) and their metabolites towards the ligand binding domain (LBD) of the androgen receptor (AR) in three distantly related species: human, rat, and zebrafish. We computed the affinity for all the selected molecules following a computational approach based on molecular modelling and docking. Three different classes of molecules with well-known endocrine activity (iprodione, procymidone, vinclozolin, and a selection of their metabolites) were evaluated. Our approach was demonstrated useful as the first step of chemical safety evaluation since ligand-target interaction is a necessary condition for exerting any biological effect. Moreover, a different sensitivity concerning AR LBD was computed for the tested species (rat being the least sensitive of the three). This evidence suggests that, in order not to over-/under-estimate the risks connected with the use of a chemical entity, further in vitro and/or in vivo tests should be carried out only after an accurate evaluation of the most suitable cellular system or animal species. The introduction of in silico approaches to evaluate hazard can accelerate discovery and innovation with a lower economic effort than with a fully wet strategy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping