Docking and QSAR study on the binding interactions between polycyclic aromatic hydrocarbons and estrogen receptor

Li, Fēi; Wu, Huifeng; Li, Lianzhen; Li, Xuehua; Zhao, Jianmin; Peijnenburg, Willie J.G.M.

doi:10.1016/j.ecoenv.2012.03.009

Cited by 38 publications

(22 citation statements)

References 45 publications

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“…Molecular docking ( in silico ) studies have the efficiency to predict possible interactions of the ligands with the receptors for elucidating molecular cross‐talks within the human system (Jacobs, ). Certain molecular docking studies revealed possible interactions of receptors with several agonists and antagonists (Li et al ., ). Molecular linkages of PAEs and their monophthalates could be predicted by molecular docking studies (Shyu et al ., ) with hPPARs and hRXRs.…”

Section: Introductionmentioning

confidence: 97%

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Josh

Pradeep

Amma

et al. 2013

J of Applied Toxicology

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This exhaustive in silico study looks into the molecular interactions of phthalates and their metabolites with human peroxisome proliferator-activated receptor (hPPAR) and retinoid X receptor (hRXR) α, β and γ subtypes--the nuclear receptor proteins function as transcription factors by regulating the expression of downstream genes. Apart from the much discussed plasticizer bisphenol A, we examined the binding affinities of 15 common diphthalates and their monophthalates, natural (linoleic acid, conjugated linoleic acid) and synthetic (bezafibrate, pioglitazone, GW 50156) ligands with hPPARs. In addition to these phthalates, specific natural (retinoic and phytanic acids) and synthetic (bexarotene, rosiglitazone) ligands were examined with hRXRs. The Maestro, Schrödinger Suite 2012 was used for the molecular docking study. In general, natural ligands of hPPAR showed less binding efficiencies than phthalic acid esters and drugs. The diphthalate di-iso-decyl phthalate showed the highest G score (-9.99) with hPPAR (γ), while its monophthalate (mono-iso-decyl phthalate) showed a comparatively less G score (-9.56). Though the PPAR modulator GW 50156 showed strong affinity with all hPPAR subtypes, its highest G score (-12.43) was with hPPARβ. Hazardous di(2-ethylhexyl)phthalate generally showed a greater preference to hRXRs than hPPARs, but its highest G score (-10.87) was with hRXRα; while its monophthalate (Mono(2-ethylhexyl)phthalate) showed a lesser G score (-8.59). The drug bexarotene showed the highest G score (-13.32) with hRXRβ. Moreover, bisphenol A showed more affinity towards hRXR. Briefly, this study gives an overview on the preference of phthalic acid esters, natural and synthetic ligands on to hPPAR and hRXR subtypes, which would lead to further in vitro mechanistic as well as in vivo preclinical and clinical studies.

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Section: Introductionmentioning

confidence: 97%

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Josh

Pradeep

Amma

et al. 2013

J of Applied Toxicology

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“…12 PAHs may have potential endocrine disrupting capabilities. Urinary metabolites of PAHs (e.g., metabolites of naphthalene, fluorene, phenanthrene, pyrene) are shown to bind to estrogen receptors, 13 to have estrogenic activity, 14 – 16 and may be thyroid receptor antagonists. 17 …”

Section: Introductionmentioning

confidence: 99%

Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls

Dobraca

Laurent

Greenspan

et al. 2020

Environmental Epidemiology

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“…failed to include any validation data [66] or did not define an AD that would allow us to evaluate their suitability to OH-PCB-like structures [35,42,52,[66][67][68][69][70][71][72][73][74]. Our models were derived using data from a specific in vitro screening assay, use modelling approaches that, with the same software and training set, can be reproduced exactly, clearly report performance characteristics in widely accepted metrics from a test set of molecules naieve to the models, have a well-defined (albeit limited) AD, and are interpretable with respect to the molecular descriptors contributing to estrogenicity potency.…”

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confidence: 99%

Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis^∗

Ruíz

Myshkin

Quigley

et al. 2013

SAR and QSAR in Environmental Research

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Alternative methods, including quantitative structure-activity relationships (QSAR), are being used increasingly when appropriate data for toxicity evaluation of chemicals are not available. Approximately 40 mono-hydroxylated polychlorinated biphenyls (OH-PCBs) have been identified in humans. They represent a health and environmental concern because some of them have been shown to have agonist or antagonist interactions with human hormone receptors. This could lead to modulation of steroid hormone receptor pathways and endocrine system disruption. We performed QSAR analyses using available estrogenic activity (human estrogen receptor ER alpha) data for 71 OH-PCBs. The modelling was performed using multiple molecular descriptors including electronic, molecular, constitutional, topological, and geometrical endpoints. Multiple linear regressions and recursive partitioning were used to best fit descriptors. The results show that the position of the hydroxyl substitution, polarizability, and meta adjacent un-substituted carbon pairs at the phenolic ring contribute towards greater estrogenic activity for these chemicals. These comparative QSAR models may be used for predictive toxicity, and identification of health consequences of PCB metabolites that lack empirical data. Such information will help prioritize such molecules for additional testing, guide future basic laboratory research studies, and help the health/risk assessment community understand the complex nature of chemical mixtures.

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Docking and QSAR study on the binding interactions between polycyclic aromatic hydrocarbons and estrogen receptor

Cited by 38 publications

References 45 publications

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls

Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis^∗

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Docking and QSAR study on the binding interactions between polycyclic aromatic hydrocarbons and estrogen receptor

Cited by 38 publications

References 45 publications

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach

Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls

Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis∗

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Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis^∗