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
  • 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.