論文

査読有り
2018年5月1日

Synthesis and biological evaluation of histone deacetylase and DNA topoisomerase II-Targeted inhibitors

Bioorganic and Medicinal Chemistry
  • Mitsuaki Yamashita
  • ,
  • Teruyuki Tahara
  • ,
  • Shinya Hayakawa
  • ,
  • Hironobu Matsumoto
  • ,
  • Shun-ichi Wada
  • ,
  • Kiyoshi Tomioka
  • ,
  • Akira Iida

26
8
開始ページ
1920
終了ページ
1928
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bmc.2018.02.042
出版者・発行元
Elsevier Ltd

HDAC inhibitors enable histones to maintain a high degree of acetylation. The resulting looser state of chromatin DNA may increase the accessibility of DNA drug targets and consequently improve the efficiency of anticancer drugs targeting DNA, such as Topo II inhibitors. A novel class of nucleoside-SAHA derivatives has been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities toward histone deacetylases and Topo II, and their cytotoxicities in cancer cell lines, were evaluated. Among the synthesized hybrid compounds, compound 16b showed the potent HDAC inhibitory activity at a low nanomolar level and exhibited antiproliferative activity toward cancer cell lines including MCF-7 (breast), HCT-116 (colon), and DU-145 (prostate) cancer cells at a low micromolar level. Moreover, compound 16a showed HDAC6-selectivity 20-fold over HDAC1.

リンク情報
DOI
https://doi.org/10.1016/j.bmc.2018.02.042
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29519604
ID情報
  • DOI : 10.1016/j.bmc.2018.02.042
  • ISSN : 1464-3391
  • ISSN : 0968-0896
  • PubMed ID : 29519604
  • SCOPUS ID : 85042845909

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