Development of Potential Antitumor Agents. Synthesis and Biological Evaluation of a New Set of Sulfonamide Derivatives as Histone Deacetylase Inhibitors

• Published in: Journal of medicinal chemistry Vol. 46; no. 5; pp. 820 - 830
• Main Authors: Bouchain, Giliane, Leit, Silvana, Frechette, Sylvie, Khalil, Elie Abou, Lavoie, Rico, Moradei, Oscar, Woo, Soon Hyung, Fournel, Marielle, Yan, Pu T, Kalita, Ann, Trachy-Bourget, Marie-Claude, Beaulieu, Carole, Li, Zuomei, Robert, Marie-France, MacLeod, A. Robert, Besterman, Jeffrey M, Delorme, Daniel
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.02.2003; Amer Chemical Soc
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Cycle - drug effects; Cell Line; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General aspects; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacology; Life Sciences & Biomedicine; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Transplantation, Heterologous; CELLS; IN-VITRO; VIVO; SUBEROYLANILIDE HYDROXAMIC ACID; INDUCERS; ACETYLASES; TRICHOSTATIN; Antineoplastic agent; Intraperitoneal administration; Lung; Cytotoxicity; Structure activity relation; Vinylic compound; Colon; Chemical synthesis; Anilide; Tumor cell; Human; Acyltransferases; Sulfonamide; Enzyme; Transferases; Rodentia; Benzene derivatives; Hydroxamic acid; Enzyme inhibitor; Malignant tumor; Histone acetyltransferase; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Cell line; Treatment; Mouse; Animal; Carboxamide; Aromatic amine
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm020377a

A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a panel of human tumor and normal cell lines. They selectively inhibit proliferation, cause cell cycle blocks, and induce apoptosis in human cancer cells but not in normal cells. The structure−activity relationships, the antiproliferative activity, and the in vivo efficacy are described.