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

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

  • ACS Med Chem Lett. 2020 May 1;11(6):1310-1315. doi: 10.1021/acsmedchemlett.0c00153.
Yusuke Yoshikawa 1,  Airi Ishibashi 2,  Tsunayoshi Takehara 3,  Takeyuki Suzuki 3,  Kenichi Murai 1,  Yasufumi Kaneda 2,  Keisuke Nimura 2,  Mitsuhiro Arisawa 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka 565-0871, Japan.
  • 2 Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka 565-0871, Japan.
  • 3 Comprehensive Analysis Center, The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan.
PMID: 32551017 DOI: 10.1021/acsmedchemlett.0c00153
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.

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