ADME/Tox Properties and Biochemical Interactions of Silybin Congeners: In silico Study.
Nat Prod Commun
; 12(2): 175-178, 2017 Feb.
Article
en En
| MEDLINE
| ID: mdl-30428204
Silymarin, the active constituent of Silybum marianum (milk thistle), and its main component, silybin, are products with well-known hepatoprotective, cytoprotective, antioxidant, and chemopreventative properties. Despite substantial in vitro and in vivo investigations of these flavonolignans, their mechanisms of action and potential toxic effects are not fully defined. In this study we explored important ADME/Tox properties and biochemical interactions of selected flavonolignans using in silico methods. A quantitative structure-activity relationship (QSAR) model based on data from a parallel artificial membrane permeability assay (PAMPA) was used to estimate bioavailability after oral administration. Toxic effects and metabolic transformations were predicted using the knowledge-based expert systems Derek Nexus and Meteor Nexus (Lhasa Ltd). Potential estrogenic activity of the studied silybin congeners was outlined. To address further the stereospecificity of this effect the stereoisomeric forms of silybin were docked into the ligand-binding domain of the human estrogen receptor alpha (ERa) (MOE software, CCG). According to our results both stereoisomers can be accommodated into the ERa active site, but different poses and interactions were observed for silybin A and silybin B.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Silibina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Prod Commun
Asunto de la revista:
BOTANICA
/
FARMACOLOGIA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Estados Unidos