Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors

Bioorganic & Medicinal Chemistry
Xiaoyang LiYingjie Zhang

Abstract

Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC₅₀ values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor.

References

Nov 14, 2003·Journal of Medicinal Chemistry·Thomas A MillerSandro Belvedere
Nov 25, 2003·The New England Journal of Medicine·James G Herman, Stephen B Baylin
Mar 31, 2004·Journal of Molecular Biology·Ivan V GregorettiHolly V Goodson
Nov 18, 2005·Gene·Michele A GlozakEdward Seto
Sep 7, 2006·Nature Reviews. Drug Discovery·Jessica E BoldenRicky W Johnstone
Feb 3, 2007·Nature Reviews. Drug Discovery·Steven GrantPeter Kirkpatrick
Oct 24, 2007·Molecular Cancer Research : MCR·Milos DokmanovicPaul A Marks
Nov 11, 2008·Current Medicinal Chemistry·Yingjie ZhangWenfang Xu
Jun 11, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·H Miles PrinceSimon J Harrison
Oct 20, 2009·European Journal of Pharmacology·Lasse Sommer KristensenLise Lotte Hansen
Feb 4, 2010·Drugs of Today·Clara Campas-Moya
Nov 17, 2011·Journal of Biomolecular Screening·Walter Stünkel, Robert M Campbell
Mar 29, 2013·Journal of Enzyme Inhibition and Medicinal Chemistry·Lei ZhangWenfang Xu
Sep 28, 2013·Drug Discoveries & Therapeutics·Baowen Shi, Wenfang Xu
Mar 7, 2014·Current Drug Targets·Xiaoyang LiWenfang Xu
Nov 11, 2014·Drug Discoveries & Therapeutics·Xiaoyang Li, Wenfang Xu
Mar 25, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hyon-Zu LeeRichard Pazdur
May 7, 2015·Drugs·Karly P Garnock-Jones

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