title: A computational approach to evaluate the androgenic affinity of iprodione, procymidone, vinclozolin and their metabolites.
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.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Corrado Lodovico
authors.initials: CL
authors.lastname: Galli
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sensi
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Amos
authors.initials: A
authors.lastname: Fumagalli
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Chiara
authors.initials: C
authors.lastname: Parravicini
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Marina
authors.initials: M
authors.lastname: Marinovich
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
authors.forename: Ivano
authors.initials: I
authors.lastname: Eberini
mesh_terms: D000595:Amino Acid Sequence; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D006801:Humans; D006827:Hydantoins / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010080:Oxazoles / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D015027:Zebrafish
chemical_list: D001643:Bridged Bicyclo Compounds; D006827:Hydantoins; D010080:Oxazoles; D011944:Receptors, Androgen; D000620:Aminoimidazole Carboxamide; C035988:procymidone; C025643:vinclozolin; C033148:iprodione
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