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A cyclodextrin-capped histone deacetylase inhibitor |
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| Authors: | Jahangir Amin Antonino Puglisi James Clarke John Milton Minghua Wang Ronald M Paranal James E Bradner John Spencer |
| Institution: | 1. Dept. of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, East Sussex, UK;2. Oxford Nanopore Technology Ltd Edmund Cartwright House, 4 Robert Robinson Avenue, Oxford Science Park, Oxford OX4 4GA, UK;3. Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada M5S 3E1;4. Dana–Farber Cancer Institute, 44 Binney Street, Dana Building, D510D, Boston, MA 02115, USA |
| Abstract: | We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold “cap”. HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity. |
| Keywords: | HDAC Inhibitors Cyclodextrin conjugates Molecular modelling Cancer |
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