Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism
文献类型：期刊论文
| 作者 | Li, Juan; Cao, Huiming; Mu, Yunsong; Qu, Guangbo; Zhang, Aiqian; Fu, Jianjie ; Jiang, Guibin
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| 刊名 | ENVIRONMENTAL SCIENCE & TECHNOLOGY
 |
| 出版日期 | 2020-11-17 |
| 卷号 | 54期号:22页码:14525-14534 |
| ISSN号 | 0013-936X |
| 英文摘要 | Organophosphate esters (OPEs) can exhibit various toxicities including endocrine disruption activity. Unfortunately, the low-dose endocrine-disrupting effects mediated by estrogen receptors (ERs) are commonly underestimated for OPEs and their metabolites. Here, structure-oriented research was performed to investigate the estrogenic/antiestrogenic effect of 13 OPEs (including three metabolites) and the potential mechanism. All of the OPEs exerted antiestrogenic activities in both E-screen and MVLN assays. OPEs with bulky substituents, such as phenyl rings (triphenyl phosphate (TPP), tricresyl phosphate (TCP), diphenylphosphoryl chloride, and diphenylphosphite) or relatively long alkyl chains (dibutylbutylphosphonate (DBBP)), exerted relatively strong ER antagonism potency at micromolar concentrations. The established quantitative structure-activity relationship indicated that the antiestrogenic activities of the OPEs mainly depended on the volume, leading eigenvalue, and hydrophobicity of the molecule. Molecular docking revealed that the three OPEs with the bulkiest substituents on the phosphate ester group (TPP, TCP, and DBBP) have a similar interaction mode to the classical ER antagonist 4-hydroxytamoxifen. The correlation between the antiestrogenic activity and the corresponding ER binding affinity was statistically significant, strongly suggesting that the OPEs possess the classical antagonism mechanism of interfering with the positioning of helix 12 in the ER. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/44812]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Li, Juan,Cao, Huiming,Mu, Yunsong,et al. Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2020,54(22):14525-14534. |
| APA | Li, Juan.,Cao, Huiming.,Mu, Yunsong.,Qu, Guangbo.,Zhang, Aiqian.,...&Jiang, Guibin.(2020).Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism.ENVIRONMENTAL SCIENCE & TECHNOLOGY,54(22),14525-14534. |
| MLA | Li, Juan,et al."Structure-Oriented Research on the Antiestrogenic Effect of Organophosphate Esters and the Potential Mechanism".ENVIRONMENTAL SCIENCE & TECHNOLOGY 54.22(2020):14525-14534. |
入库方式： OAI收割
来源：生态环境研究中心
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