New aryldithiolethione derivatives as potent histone deacetylase inhibitors

Valerio Tazzari; Graziella Cappelletti; Manolo Casagrande; Elena Perrino; Luigi Renzi; Piero Del Soldato; Anna Sparatore

doi:10.1016/j.bmc.2010.05.011

New aryldithiolethione derivatives as potent histone deacetylase inhibitors

Bioorg Med Chem. 2010 Jun 15;18(12):4187-94. doi: 10.1016/j.bmc.2010.05.011. Epub 2010 May 7.

Authors

Valerio Tazzari¹, Graziella Cappelletti, Manolo Casagrande, Elena Perrino, Luigi Renzi, Piero Del Soldato, Anna Sparatore

Affiliation

¹ Sulfidris s.r.l., Viale Gran Sasso 17, 20131 Milan, Italy.

PMID: 20576572
DOI: 10.1016/j.bmc.2010.05.011

Abstract

A series of dithiolethione derivatives was synthesized and the in vitro HDAC inhibitory activity was tested. The most active compounds, 1 and 2, exhibited an IC(50) in nM range with a strong hyperacetylation of histone H4 in A549 cells. The HDAC inhibitory activity comparable to that of SAHA and the inhibition of A549 cell proliferation suggest that these compounds are worthy of further studies as potential anticancer agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Drug Screening Assays, Antitumor
Histone Deacetylase Inhibitors / chemical synthesis
Histone Deacetylase Inhibitors / chemistry*
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylases / chemistry*
Histone Deacetylases / metabolism
Humans
Hydroxamic Acids / chemical synthesis
Hydroxamic Acids / chemistry*
Hydroxamic Acids / pharmacology
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology
Valproic Acid / chemistry

Substances

Antineoplastic Agents
Histone Deacetylase Inhibitors
Hydroxamic Acids
N-hydroxy-5-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)pentanamide
N-hydroxy-7-(4-(3-thioxo-3H-1,2-dithiol-5-yl)phenoxy)heptanamide
Thiophenes
Valproic Acid
Histone Deacetylases