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

doi:10.1016/j.bmcl.2007.06.038

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

Faculty of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

48 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 p21^WAF1/CIP1 expression than the clinically used HDAC inhibitor suberoylanilide hydroxamic acid (Zolinza™).

Original language	English
Pages (from-to)	4895-4900
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2007.06.038
Publication status	Published - Sept 1 2007

Keywords

HDAC
HDAC inhibitor
Hydroxamic acid
Isoindoklinone
Pancreatic cancer
p21

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2007.06.038

Cite this

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

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{\texttrademark}).",

keywords = "HDAC, HDAC inhibitor, Hydroxamic acid, Isoindoklinone, Pancreatic cancer, p21",

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

note = "Funding Information: The work described in this paper was partially supported by a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors thank Prof. Nishino, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, for data on the HDAC inhibitory activity of Zolinza, and Dr. Keisuke Imai, Lead Discovery Research Labs., Astellas Pharma Inc., for computational docking studies. ",

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doi = "10.1016/j.bmcl.2007.06.038",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors

AU - Lee, Shoukou

AU - Shinji, Chihiro

AU - Ogura, Kiyoshi

AU - Shimizu, Motomu

AU - Maeda, Satoko

AU - Sato, Mayumi

AU - Yoshida, Minoru

AU - Hashimoto, Yuichi

AU - Miyachi, Hiroyuki

N1 - Funding Information: The work described in this paper was partially supported by a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors thank Prof. Nishino, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, for data on the HDAC inhibitory activity of Zolinza, and Dr. Keisuke Imai, Lead Discovery Research Labs., Astellas Pharma Inc., for computational docking studies.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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™).

AB - 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™).

KW - HDAC

KW - HDAC inhibitor

KW - Hydroxamic acid

KW - Isoindoklinone

KW - Pancreatic cancer

KW - p21

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SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

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IS - 17

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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