Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

In this study, we explored Heck- and Suzuki-coupling methodology to modify the template 2,5-di-tert-butylhydroquinone (BHQ, 2), an inhibitor of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). We found that by utilizing Suzuki coupling, we could successfully attach a six-carbon tether...

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Autores principales: Kempton, Robert J, Kidd-Kautz, Taylor A, Laurenceau, Soizic, Paula, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2019
Materias:
Full Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541364/
https://www.ncbi.nlm.nih.gov/pubmed/31164934
http://dx.doi.org/10.3762/bjoc.15.94
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author Kempton, Robert J
Kidd-Kautz, Taylor A
Laurenceau, Soizic
Paula, Stefan
author_facet Kempton, Robert J
Kidd-Kautz, Taylor A
Laurenceau, Soizic
Paula, Stefan
author_sort Kempton, Robert J
collection PubMed
description In this study, we explored Heck- and Suzuki-coupling methodology to modify the template 2,5-di-tert-butylhydroquinone (BHQ, 2), an inhibitor of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). We found that by utilizing Suzuki coupling, we could successfully attach a six-carbon tether to BHQ that terminated in a leucine moiety to obtain target 14. Similar to related compounds based on the structure of the natural product thapsigargin, 14 displayed inhibitory potency against SERCA activity. This makes 14 a suitable candidate for the future attachment of a deactivating peptide to convey specificity for prostate cancer cells.
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spelling pubmed-65413642019-06-04 Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase Kempton, Robert J Kidd-Kautz, Taylor A Laurenceau, Soizic Paula, Stefan Beilstein J Org Chem Full Research Paper In this study, we explored Heck- and Suzuki-coupling methodology to modify the template 2,5-di-tert-butylhydroquinone (BHQ, 2), an inhibitor of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). We found that by utilizing Suzuki coupling, we could successfully attach a six-carbon tether to BHQ that terminated in a leucine moiety to obtain target 14. Similar to related compounds based on the structure of the natural product thapsigargin, 14 displayed inhibitory potency against SERCA activity. This makes 14 a suitable candidate for the future attachment of a deactivating peptide to convey specificity for prostate cancer cells. Beilstein-Institut 2019-04-24 /pmc/articles/PMC6541364/ /pubmed/31164934 http://dx.doi.org/10.3762/bjoc.15.94 Text en Copyright © 2019, Kempton et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Kempton, Robert J
Kidd-Kautz, Taylor A
Laurenceau, Soizic
Paula, Stefan
Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title_full Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title_fullStr Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title_full_unstemmed Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title_short Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase
title_sort heck- and suzuki-coupling approaches to novel hydroquinone inhibitors of calcium atpase
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541364/
https://www.ncbi.nlm.nih.gov/pubmed/31164934
http://dx.doi.org/10.3762/bjoc.15.94
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