Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 25, Issue 12, Pages 2981-2994Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2017.03.036
Keywords
Anticancer; Epigenetics; HDAC inhibitors; Isatin
Funding
- National Natural Science Foundation of China [21302111, 81373282]
- National High Tech R&D Program of China (863 Program) [2014AA020523]
- Young Scholars Program of Shandong University (YSPSDU) [2016WLJH33]
- Science and Technology of Shandong Province [2015ZDJS04001]
- National Cancer Institute of the National Institute of Health [R01CA163452]
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As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605 mu M, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311 mu M for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity. (C) 2017 Published by Elsevier Ltd.
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