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Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment.

ABSTRACT: We designed and synthesized a novel 1,2-deoxy-pyranose and terminal epoxide methyl substituted derivatives of spliceostatin A using Julia-Kocienski olefination as a key step. With respect to the biological activity, the 1,2-deoxy-pyranose analogue of spliceostatin A suppressed AR-V7 expression at the nano level (IC₅₀ = 3.3 nM). In addition, the in vivo toxicity test showed that the 1,2-deoxy-pyranose analogue was able to avoid severe toxicity compared to spliceostatin A.

SUBMITTER: Yoshikawa Y

PROVIDER: S-EPMC7294732 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment.

Yoshikawa Yusuke Y Ishibashi Airi A Takehara Tsunayoshi T Suzuki Takeyuki T Murai Kenichi K Kaneda Yasufumi Y Nimura Keisuke K Arisawa Mitsuhiro M

ACS medicinal chemistry letters 20200501 6

We designed and synthesized a novel 1,2-deoxy-pyranose and terminal epoxide methyl substituted derivatives of spliceostatin A using Julia-Kocienski olefination as a key step. With respect to the biological activity, the 1,2-deoxy-pyranose analogue of spliceostatin A suppressed AR-V7 expression at the nano level (IC50 = 3.3 nM). In addition, the in vivo toxicity test showed that the 1,2-deoxy-pyranose analogue was able to avoid severe toxicity compared to spliceostatin A. ...[more]

PMID: 32551017

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