title: Accessing the molecular interactions of phthalates and their primary metabolites with the human pregnane X receptor using in silico profiling.
abstract: Phthalates are known to cause endocrine disruption in humans and animals. Being lipophilic xenobiotic chemicals, phthalates from the surrounding environments can easily be absorbed into the biological system, thereby causing various health dysfunctions. This molecular docking study evaluates a variety of molecular interactions of 12 commonly used diphthalates and respective monophthalates onto the ligand binding domain (LBD) of the human pregnane X receptor (hPXR), a xenosensor, which would be beneficial for further in vitro and in vivo studies on hazardous phthalates. Out of 12 diphthalates and their monophthalates tested, diisodecyl phthalate (-9.16 kcal mol-1) showed more affinity toward hPXR whereas diisononyl phthalate (-8.77) and di(2-ethyhexyl)phthalate (-8.56), the predominant plasticizers found in a variety of plastics and allied products, showed comparable binding scores with that of the control ligands such as hyperforine (-9.99) and dexamethasone (-7.36). In addition to the above diphthalates, some of their monophthalates (monoisodecyl phthalate, mono-2-etheylhexyl phthalate, etc.) also established similar interactions with certain crucial amino acids in the LBD, which led to higher G scores. In fact, bisphenol A, a well-studied and proven endocrine disruptor, showed lesser G scores (-6.69) than certain phthalates. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Enzyme Technology Laboratory, Biotechnology Division, Department of Botany, University of Calicut, Kerala, 673 635, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Sarath Josh
authors.affiliation: Enzyme Technology Laboratory, Biotechnology Division, Department of Botany, University of Calicut, Kerala, 673 635, India.
authors.forename: S
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Chemistry, University of Calicut, Kerala, 673 635, India.
authors.forename: Aparna K
authors.initials: AK
authors.lastname: Balan
authors.affiliation: Centre for Cheminformatics, Department of Chemistry, Malabar Christian College, University of Calicut, Kozhikode, Kerala, 673 001, India.
authors.forename: M N
authors.initials: MN
authors.lastname: Sreejith
authors.affiliation: Enzyme Technology Laboratory, Biotechnology Division, Department of Botany, University of Calicut, Kerala, 673 635, India. benjamin@uoc.ac.in.
authors.forename: Sailas
authors.initials: S
authors.lastname: Benjamin
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D052244:Endocrine Disruptors / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D010795:Phthalic Acids / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D000077297:Pregnane X Receptor; D011485:Protein Binding; D011987:Receptors, Steroid / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D052244:Endocrine Disruptors; D008024:Ligands; D010795:Phthalic Acids; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid
keywords: Glide; bisphenol A; endocrine disrupting compounds; human pregnane X receptor; in silico profiling; phthalates