Aromatic sulfide inhibitors of histone deacetylase based on arylsulfinyl-2,4-hexadienoic acid hydroxyamides.
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.
Marson
Charles M
CM
Department of Chemistry, University College London, Christopher Ingold Laboratories, London WC1H OAJ, UK. c.m.marson@ucl.ac.uk
Savy
Pascal
P
Rioja
Alphonso S
AS
Mahadevan
Thevaki
T
Mikol
Catherine
C
Veerupillai
Arthi
A
Nsubuga
Eva
E
Chahwan
Angela
A
Joel
Simon P
SP
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis* / Q000494:pharmacology; D013441:Sulfinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
D000577:Amides; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D013440:Sulfides; D013441:Sulfinic Acids; D013011:Sorbic Acid