Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors

Shoukou Lee, Chihiro Shinji, Kiyoshi Ogura, Motomu Shimizu, Satoko Maeda, Mayumi Sato, Minoru Yoshida, Yuichi Hashimoto, Hiroyuki Miyachi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We designed and synthesized hydroxamic acid derivatives bearing a 4-(3-pyridyl)phenyl group as a cap structure, and found that they exhibit potent histone deacetylase (HDAC) inhibitory activity. A representative compound, 17a, showed more potent growth-inhibitory activity against pancreatic cancer cells and greater upregulation of p21WAF1/CIP1 expression than the clinically used HDAC inhibitor suberoylanilide hydroxamic acid (Zolinza™).

Original languageEnglish
Pages (from-to)4895-4900
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number17
DOIs
Publication statusPublished - Sep 1 2007
Externally publishedYes

Fingerprint

Hydroxamic Acids
Histone Deacetylase Inhibitors
Bearings (structural)
Derivatives
Histone Deacetylases
Pancreatic Neoplasms
Up-Regulation
Cells
Growth
vorinostat

Keywords

  • HDAC
  • HDAC inhibitor
  • Hydroxamic acid
  • Isoindoklinone
  • p21
  • Pancreatic cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. / Lee, Shoukou; Shinji, Chihiro; Ogura, Kiyoshi; Shimizu, Motomu; Maeda, Satoko; Sato, Mayumi; Yoshida, Minoru; Hashimoto, Yuichi; Miyachi, Hiroyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 17, 01.09.2007, p. 4895-4900.

Research output: Contribution to journalArticle

Lee, S, Shinji, C, Ogura, K, Shimizu, M, Maeda, S, Sato, M, Yoshida, M, Hashimoto, Y & Miyachi, H 2007, 'Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 17, pp. 4895-4900. https://doi.org/10.1016/j.bmcl.2007.06.038
Lee, Shoukou ; Shinji, Chihiro ; Ogura, Kiyoshi ; Shimizu, Motomu ; Maeda, Satoko ; Sato, Mayumi ; Yoshida, Minoru ; Hashimoto, Yuichi ; Miyachi, Hiroyuki. / Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 17. pp. 4895-4900.
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AU - Maeda, Satoko

AU - Sato, Mayumi

AU - Yoshida, Minoru

AU - Hashimoto, Yuichi

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