Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin AElectronic supplementary information (ESI) available: Synthetic procedures and spectral data of compounds 3, 4, 5, 6, 7 and 8, and bioassay results. See DOI: 10.1039/c3cc41422a

Eight N -(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of them were active in the nanomolar range (IC 50 = 1.9-22 nM...

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Bibliographic Details
Main Authors De Vreese, Rob, Verhaeghe, Tom, Desmet, Tom, D'hooghe, Matthias
Format Journal Article
LanguageEnglish
Published 09.04.2013
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Summary:Eight N -(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of them were active in the nanomolar range (IC 50 = 1.9-22 nM). Further analysis revealed that the sulfone derivatives (designated as Tubathians) are superior to their non-oxidized sulfide analogues, and the two most active sulfones showed good to excellent HDAC6 selectivity compared to all other HDAC isoform classes. Two analogues of Tubastatin A bearing a sulfone moiety were shown to display potent and selective HDAC6 inhibition in the nanomolar range.
Bibliography:3
Electronic supplementary information (ESI) available: Synthetic procedures and spectral data of compounds
and bioassay results. See DOI
4
5
6
and
10.1039/c3cc41422a
7
8
,
ISSN:1359-7345
1364-548X
DOI:10.1039/c3cc41422a