Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10
17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a steroidogenesis enzyme known for its potential role in Alzheimer’s disease. For comparison purposes between steroidal and nonsteroidal 17β-HSD10 inhibitors 1 and 2, respectively, we attempted the chemical...
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| Language: | English |
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MDPI AG
2018-07-01
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| Series: | Magnetochemistry |
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| Online Access: | http://www.mdpi.com/2312-7481/4/3/32 |
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| author | Sophie Boutin Donald Poirier |
| author_facet | Sophie Boutin Donald Poirier |
| author_sort | Sophie Boutin |
| collection | DOAJ |
| description | 17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a steroidogenesis enzyme known for its potential role in Alzheimer’s disease. For comparison purposes between steroidal and nonsteroidal 17β-HSD10 inhibitors 1 and 2, respectively, we attempted the chemical synthesis of benzothiazole phosphonate derivative 2. Instead of a one-pot synthesis, we report a two-step synthesis with characterization of both imine intermediate 5 and final compound 2. Furthermore, complete assignation of 1H and 13C nuclear magnetic resonance (NMR) signals of 2 is provided, as we observed a divergence of NMR data with those published previously. Finally, biological assays showed that 1 and 2 inhibited the oxidation of estradiol (E2) into estrone (E1) by the 17β-HSD10 recombinant protein. However, in human embryonic kidney (HEK)-293 intact cells transfected with 17β-HSD10, only the steroidal inhibitor 1 induced a dose-dependent inhibition of E2 to E1 transformation. |
| first_indexed | 2024-12-10T14:42:06Z |
| format | Article |
| id | doaj.art-0c70c82b83fd48fabdc8284ddc613a25 |
| institution | Directory Open Access Journal |
| issn | 2312-7481 |
| language | English |
| last_indexed | 2024-12-10T14:42:06Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
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| series | Magnetochemistry |
| spelling | doaj.art-0c70c82b83fd48fabdc8284ddc613a252022-12-22T01:44:39ZengMDPI AGMagnetochemistry2312-74812018-07-01433210.3390/magnetochemistry4030032magnetochemistry4030032Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10Sophie Boutin0Donald Poirier1Endocrinology and Nephrology Unit, Laboratory of Medicinal Chemistry, CHU de Québec—Research Center, Québec, QC G1V 4G2, CanadaEndocrinology and Nephrology Unit, Laboratory of Medicinal Chemistry, CHU de Québec—Research Center, Québec, QC G1V 4G2, Canada17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a steroidogenesis enzyme known for its potential role in Alzheimer’s disease. For comparison purposes between steroidal and nonsteroidal 17β-HSD10 inhibitors 1 and 2, respectively, we attempted the chemical synthesis of benzothiazole phosphonate derivative 2. Instead of a one-pot synthesis, we report a two-step synthesis with characterization of both imine intermediate 5 and final compound 2. Furthermore, complete assignation of 1H and 13C nuclear magnetic resonance (NMR) signals of 2 is provided, as we observed a divergence of NMR data with those published previously. Finally, biological assays showed that 1 and 2 inhibited the oxidation of estradiol (E2) into estrone (E1) by the 17β-HSD10 recombinant protein. However, in human embryonic kidney (HEK)-293 intact cells transfected with 17β-HSD10, only the steroidal inhibitor 1 induced a dose-dependent inhibition of E2 to E1 transformation.http://www.mdpi.com/2312-7481/4/3/32NMRchemical synthesisenzyme inhibitor17β-HSD10Alzheimer’s |
| spellingShingle | Sophie Boutin Donald Poirier Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 Magnetochemistry NMR chemical synthesis enzyme inhibitor 17β-HSD10 Alzheimer’s |
| title | Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 |
| title_full | Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 |
| title_fullStr | Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 |
| title_full_unstemmed | Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 |
| title_short | Structure Confirmation and Evaluation of a Nonsteroidal Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 10 |
| title_sort | structure confirmation and evaluation of a nonsteroidal inhibitor of 17β hydroxysteroid dehydrogenase type 10 |
| topic | NMR chemical synthesis enzyme inhibitor 17β-HSD10 Alzheimer’s |
| url | http://www.mdpi.com/2312-7481/4/3/32 |
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