Aromatic Sulfide Inhibitors of Histone Deacetylase Based on Arylsulfinyl-2,4-hexadienoic Acid Hydroxyamides
Journal of Medicinal Chemistry2005Vol. 49(2), pp. 800–805
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Charles M. Marson, Pascal Savy, Alphonso S. Rioja, Thevaki Mahadevan, Catherine Mikol, Arthi Veerupillai, Eva Nsubuga, Angela Chahwan, Simon P. Joel
Abstract
The synthesis of a novel series of potent inhibitors of histone deacetylases is described, based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides and their derivatives. In vitro IC(50) values down to 40 nM were obtained, and several compounds showed inhibition of CEM (human leukemic) cell viability with IC(50) of approximately 1.5 microM, comparable to or better than that of suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase currently in clinical trials.
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