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 synthesis of benzothiazole phosphonat...

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Bibliographic Details
Published in:Magnetochemistry 2018-09, Vol.4 (3), p.32
Main Authors: Boutin, Sophie, Poirier, Donald
Format: Article
Language:English
Subjects:
17β-HSD10
Alzheimer’s
Chemical synthesis
Dehydrogenases
Disease
Divergence
enzyme inhibitor
Enzymes
Hydroxysteroids
Inhibitors
Kidneys
NMR
Nuclear magnetic resonance
Organic chemistry
Oxidation
Proteins
Sex hormones
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Summary: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.
ISSN:2312-7481
2312-7481
DOI:10.3390/magnetochemistry4030032