title: Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors.
abstract: We designed and synthesized hydroxamic acid derivatives bearing a 4-(3-pyridyl)phenyl group as a cap structure, and found that they exhibit potent histone deacetylase (HDAC) inhibitory activity. A representative compound, 17a, showed more potent growth-inhibitory activity against pancreatic cancer cells and greater upregulation of p21(WAF1/CIP1) expression than the clinically used HDAC inhibitor suberoylanilide hydroxamic acid (Zolinza).
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi, Tokyo, Japan.
authors.forename: Shoukou
authors.initials: S
authors.lastname: Lee
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shinji
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ogura
authors.forename: Motomu
authors.initials: M
authors.lastname: Shimizu
authors.forename: Satoko
authors.initials: S
authors.lastname: Maeda
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D015854:Up-Regulation; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077337:Vorinostat