Aromatic Sulfide Inhibitors of Histone Deacetylase Based on Arylsulfinyl-2,4-hexadienoic Acid Hydroxyamides

• Published in: Journal of medicinal chemistry Vol. 49; no. 2; pp. 800 - 805
• Main Authors: Marson, Charles M, Savy, Pascal, Rioja, Alphonso S, Mahadevan, Thevaki, Mikol, Catherine, Veerupillai, Arthi, Nsubuga, Eva, Chahwan, Angela, Joel, Simon P
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.01.2006; Amer Chemical Soc
• Subjects: Amides - chemical synthesis; Amides - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Chemistry, Medicinal; Drug Screening Assays, Antitumor; General aspects; Histone Deacetylase Inhibitors; Humans; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Sorbic Acid - analogs & derivatives; Sorbic Acid - chemical synthesis; Sorbic Acid - pharmacology; Structure-Activity Relationship; Sulfides - chemical synthesis; Sulfides - pharmacology; Sulfinic Acids - chemical synthesis; Sulfinic Acids - pharmacology; IN-VITRO; POTENT; TSA; VIVO; AMIDE ANALOGS; DIFFERENTIATION; INDUCERS; ACETYLASES; CANCER; TRICHOSTATIN; Antineoplastic agent; Histone deacetylase inhibitor; Enzyme; Hydroxamic acid; Enzyme inhibitor; Sulfoxide; Benzenic compound; Hydrolases; Aromatic compound; Dienic compound; In vitro; Organic sulfide
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm051010j

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 IC50 values down to 40 nM were obtained, and several compounds showed inhibition of CEM (human leukemic) cell viability with IC50 of ∼1.5 μM, comparable to or better than that of suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase currently in clinical trials.