In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors
Background. Poisoning from pesticides can be extremely hazardous for non-invasive species, such as bees, and humans causing nearly 300,000 deaths worldwide every year. Several pesticides are recognized as endocrine disruptors compounds that alter the production of the normal hormones mainly by actin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7751 |
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| author | Giulia Spaggiari Nadia Iovine Pietro Cozzini |
| author_facet | Giulia Spaggiari Nadia Iovine Pietro Cozzini |
| author_sort | Giulia Spaggiari |
| collection | DOAJ |
| description | Background. Poisoning from pesticides can be extremely hazardous for non-invasive species, such as bees, and humans causing nearly 300,000 deaths worldwide every year. Several pesticides are recognized as endocrine disruptors compounds that alter the production of the normal hormones mainly by acting through their interaction with nuclear receptors (NRs). Among the insecticides, one of the most used is pyriproxyfen. As analogous to the juvenile hormone, the pyriproxyfen acts in the bee’s larval growth and creates malformations at the adult organism level. Methods. This work aims to investigate the possible negative effects of pyriproxyfen and its metabolite, the 4′-OH-pyriproxyfen, on human and bee health. We particularly investigated the mechanism of binding of pyriproxyfen and its metabolite with ultraspiracle protein/ecdysone receptor (USP-EcR) dimer of <i>A. mellifera</i> and the relative heterodimer farnesoid X receptor/retinoid X receptor alpha (FXR-RXRα) of <i>H. sapiens</i> using molecular dynamic simulations. Results. The results revealed that pyriproxyfen and its metabolite, the 4′-OH- pyriproxyfen, stabilize each dimer and resulted in stronger binders than the natural ligands. Conclusion. We demonstrated the endocrine interference of two pesticides and explained their possible mechanism of action. Furthermore, in vitro studies should be carried out to evaluate the biological effects of pyriproxyfen and its metabolite. |
| first_indexed | 2024-03-10T09:36:45Z |
| format | Article |
| id | doaj.art-df536d9e608d4e2b8f90e5453d8dcefb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:45Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-df536d9e608d4e2b8f90e5453d8dcefb2023-11-22T04:03:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214775110.3390/ijms22147751In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> ReceptorsGiulia Spaggiari0Nadia Iovine1Pietro Cozzini2Molecular Modeling Lab, Department of Food and Drug, University of Parma, Parco Area Delle Scienze 17/A, I-43124 Parma, ItalyMolecular Modeling Lab, Department of Food and Drug, University of Parma, Parco Area Delle Scienze 17/A, I-43124 Parma, ItalyMolecular Modeling Lab, Department of Food and Drug, University of Parma, Parco Area Delle Scienze 17/A, I-43124 Parma, ItalyBackground. Poisoning from pesticides can be extremely hazardous for non-invasive species, such as bees, and humans causing nearly 300,000 deaths worldwide every year. Several pesticides are recognized as endocrine disruptors compounds that alter the production of the normal hormones mainly by acting through their interaction with nuclear receptors (NRs). Among the insecticides, one of the most used is pyriproxyfen. As analogous to the juvenile hormone, the pyriproxyfen acts in the bee’s larval growth and creates malformations at the adult organism level. Methods. This work aims to investigate the possible negative effects of pyriproxyfen and its metabolite, the 4′-OH-pyriproxyfen, on human and bee health. We particularly investigated the mechanism of binding of pyriproxyfen and its metabolite with ultraspiracle protein/ecdysone receptor (USP-EcR) dimer of <i>A. mellifera</i> and the relative heterodimer farnesoid X receptor/retinoid X receptor alpha (FXR-RXRα) of <i>H. sapiens</i> using molecular dynamic simulations. Results. The results revealed that pyriproxyfen and its metabolite, the 4′-OH- pyriproxyfen, stabilize each dimer and resulted in stronger binders than the natural ligands. Conclusion. We demonstrated the endocrine interference of two pesticides and explained their possible mechanism of action. Furthermore, in vitro studies should be carried out to evaluate the biological effects of pyriproxyfen and its metabolite.https://www.mdpi.com/1422-0067/22/14/7751molecular dynamic simulationscomputational methodsnuclear receptorsbeesendocrine disruptors compoundspesticides |
| spellingShingle | Giulia Spaggiari Nadia Iovine Pietro Cozzini In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors International Journal of Molecular Sciences molecular dynamic simulations computational methods nuclear receptors bees endocrine disruptors compounds pesticides |
| title | In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors |
| title_full | In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors |
| title_fullStr | In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors |
| title_full_unstemmed | In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors |
| title_short | In Silico Prediction of the Mechanism of Action of Pyriproxyfen and 4′-OH-Pyriproxyfen against <i>A. mellifera</i> and <i>H. sapiens</i> Receptors |
| title_sort | in silico prediction of the mechanism of action of pyriproxyfen and 4 oh pyriproxyfen against i a mellifera i and i h sapiens i receptors |
| topic | molecular dynamic simulations computational methods nuclear receptors bees endocrine disruptors compounds pesticides |
| url | https://www.mdpi.com/1422-0067/22/14/7751 |
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