Histone Deacetylase 2 (HDAC2) Inhibitors Containing Boron |
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Authors: | Poya Kavianpour Madeleine C M Gemmell Dr Jan U Kahlert Prof Louis M Rendina |
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Affiliation: | School of Chemistry, The University of Sydney, The University of Sydney, F11, Eastern Avenue, Sydney, NSW 2006 Australia |
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Abstract: | Histone deacetylase enzymes (HDACs) are responsible for the global silencing of tumour-suppressor genes. Treatment with a histone deacetylase inhibitor (HDACi) can reverse this process and restore normal cell function. Herein, we report a small series of boron-based (boronic acid, boronate ester and closo-1,2-carborane) HDAC2 inhibitors with IC50 values in the nanomolar range. The boronate ester 4 b was the most potent compound assessed in this study (IC50=40.6±1.5 nM), followed closely by the 1,2-closo-carborane (IC50=42.9±1.5 nM). Compound 4 b exceeds the potency of the related gold-standard HDAC pan-inhibitor vorinostat ( 1 ) toward this particular HDAC isoform. |
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Keywords: | boron cancer epigenetics HDAC inhibitors vorinostat |
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