Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors |
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Authors: | Lee Shoukou Shinji Chihiro Ogura Kiyoshi Shimizu Motomu Maeda Satoko Sato Mayumi Yoshida Minoru Hashimoto Yuichi Miyachi Hiroyuki |
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Affiliation: | Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo, Japan. |
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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). |
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