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

ABSTRACT: 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.

SUBMITTER: Kempton RJ

PROVIDER: S-EPMC6541364 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Kempton Robert J RJ Kidd-Kautz Taylor A TA Laurenceau Soizic S Paula Stefan S

Beilstein journal of organic chemistry 20190424

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 inhibi ...[more]

PMID: 31164934

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