Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors
Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors
There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric(thiol) form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and enzymatic inhibitory activity against recombinant HDAC1. The latter effect is surprising since previous SAR suggested that modification of the thiol functionality should detrimentally affect HDAC potency. We therefore also report our preliminary studies on the mechanism of action of this observed effect.
81-88
Baud, Matthias
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Leiser, Thomas
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Petrucci, Vanessa
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Gunaratnam, Mekala
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Neidle, Stephen
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Meyer-Almes, Franz-Josef
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Fuchter, Matthew J.
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Baud, Matthias
8752d519-3d33-43b6-9a77-ab731d410c2e
Leiser, Thomas
0a989c0c-4a10-4fb3-95eb-e7f511229e14
Petrucci, Vanessa
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Gunaratnam, Mekala
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Neidle, Stephen
edf2d7ee-a257-4d4c-a3ea-b3c9c42b5ff3
Meyer-Almes, Franz-Josef
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Fuchter, Matthew J.
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Baud, Matthias, Leiser, Thomas, Petrucci, Vanessa, Gunaratnam, Mekala, Neidle, Stephen, Meyer-Almes, Franz-Josef and Fuchter, Matthew J.
(2013)
Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors.
Beilstein Journal of Organic Chemistry, 9, .
(doi:10.3762/bjoc.9.11).
(PMID:23400330)
Abstract
There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric(thiol) form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and enzymatic inhibitory activity against recombinant HDAC1. The latter effect is surprising since previous SAR suggested that modification of the thiol functionality should detrimentally affect HDAC potency. We therefore also report our preliminary studies on the mechanism of action of this observed effect.
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1860-5397-9-11.pdf
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Accepted/In Press date: 11 December 2012
e-pub ahead of print date: 15 January 2013
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Local EPrints ID: 400513
URI: http://eprints.soton.ac.uk/id/eprint/400513
ISSN: 1860-5397
PURE UUID: d0e4b18d-a2a6-4e1a-bbba-4e82ad1938e6
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Date deposited: 16 Sep 2016 15:54
Last modified: 15 Mar 2024 03:54
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Author:
Thomas Leiser
Author:
Vanessa Petrucci
Author:
Mekala Gunaratnam
Author:
Stephen Neidle
Author:
Franz-Josef Meyer-Almes
Author:
Matthew J. Fuchter
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