Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor
Endocrine-disrupting chemicals (EDCs) are a serious global public health and environmental concern. Pyrethroids are insecticide chemicals that are extensively used for crop protection and household purposes but have been identified as EDCs. On account of their ubiquitous environmental presence, huma...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/10/2/143 |
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| author | Ishfaq Ahmad Sheikh Mohd Amin Beg |
| author_facet | Ishfaq Ahmad Sheikh Mohd Amin Beg |
| author_sort | Ishfaq Ahmad Sheikh |
| collection | DOAJ |
| description | Endocrine-disrupting chemicals (EDCs) are a serious global public health and environmental concern. Pyrethroids are insecticide chemicals that are extensively used for crop protection and household purposes but have been identified as EDCs. On account of their ubiquitous environmental presence, human exposure occurs via food, dermal, or inhalation routes and is associated with health problems, including reproductive dysfunction. Permethrin is the most commonly used pyrethroid, and with two chiral centers in its structure, it has four stereoisomeric forms (two enantiomer pairs), i.e., permethrin (1<i>R</i>,3<i>R</i>)-<i>cis</i>, permethrin (1<i>R</i>,3<i>S</i>)-<i>trans</i>, permethrin (1<i>S</i>,3<i>S</i>)-<i>cis</i>, and permethrin (1<i>S</i>,3<i>R</i>)-<i>trans</i>. The current study was performed for predicting the potential endocrine-disrupting activity of the aforementioned four stereoisomers of permethrin against the androgen receptor (AR). The structural binding characterization and binding energy estimations in the AR binding pocket were done using induced fit docking. The structural binding data indicated that all stereoisomers were placed stably in the AR binding pocket and that the estimated binding energy values were comparable to the AR native ligand, except for permethrin (1<i>S</i>,3<i>S</i>)-<i>cis</i>. Furthermore, the commonality in the amino acid interactions to that of the AR native ligand and the binding energy values suggested the potential AR-disrupting activity of all the stereoisomers; however, stereoselective differences were not observed. Taken together, the results suggest that human exposure to permethrin, either as a racemate mixture or in individual stereoisomer form, could potentially interfere with AR function, which may lead to male reproductive dysfunction. |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T04:42:22Z |
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| series | Biology |
| spelling | doaj.art-d894466ead1f41309079357d79a954b52023-12-03T13:19:50ZengMDPI AGBiology2079-77372021-02-0110214310.3390/biology10020143Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen ReceptorIshfaq Ahmad Sheikh0Mohd Amin Beg1King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi ArabiaKing Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi ArabiaEndocrine-disrupting chemicals (EDCs) are a serious global public health and environmental concern. Pyrethroids are insecticide chemicals that are extensively used for crop protection and household purposes but have been identified as EDCs. On account of their ubiquitous environmental presence, human exposure occurs via food, dermal, or inhalation routes and is associated with health problems, including reproductive dysfunction. Permethrin is the most commonly used pyrethroid, and with two chiral centers in its structure, it has four stereoisomeric forms (two enantiomer pairs), i.e., permethrin (1<i>R</i>,3<i>R</i>)-<i>cis</i>, permethrin (1<i>R</i>,3<i>S</i>)-<i>trans</i>, permethrin (1<i>S</i>,3<i>S</i>)-<i>cis</i>, and permethrin (1<i>S</i>,3<i>R</i>)-<i>trans</i>. The current study was performed for predicting the potential endocrine-disrupting activity of the aforementioned four stereoisomers of permethrin against the androgen receptor (AR). The structural binding characterization and binding energy estimations in the AR binding pocket were done using induced fit docking. The structural binding data indicated that all stereoisomers were placed stably in the AR binding pocket and that the estimated binding energy values were comparable to the AR native ligand, except for permethrin (1<i>S</i>,3<i>S</i>)-<i>cis</i>. Furthermore, the commonality in the amino acid interactions to that of the AR native ligand and the binding energy values suggested the potential AR-disrupting activity of all the stereoisomers; however, stereoselective differences were not observed. Taken together, the results suggest that human exposure to permethrin, either as a racemate mixture or in individual stereoisomer form, could potentially interfere with AR function, which may lead to male reproductive dysfunction.https://www.mdpi.com/2079-7737/10/2/143androgen receptorchiralityendocrine disruptionpermethrinstereoisomersreproductive dysfunction |
| spellingShingle | Ishfaq Ahmad Sheikh Mohd Amin Beg Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor Biology androgen receptor chirality endocrine disruption permethrin stereoisomers reproductive dysfunction |
| title | Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor |
| title_full | Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor |
| title_fullStr | Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor |
| title_full_unstemmed | Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor |
| title_short | Structural Aspects of Potential Endocrine-Disrupting Activity of Stereoisomers for a Common Pesticide Permethrin against Androgen Receptor |
| title_sort | structural aspects of potential endocrine disrupting activity of stereoisomers for a common pesticide permethrin against androgen receptor |
| topic | androgen receptor chirality endocrine disruption permethrin stereoisomers reproductive dysfunction |
| url | https://www.mdpi.com/2079-7737/10/2/143 |
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