title: Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors.
abstract: Histone deacetylases (HDACs) are zinc-dependent or NAD(+) dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50=10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China. Electronic address: wfxu@yahoo.cn.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China. Electronic address: xuechenl@hku.hk.
authors.forename: Xuechen
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: C000607147:4-(3-(5'-bromo-2'-oxospiro((1,3)dioxane-2,3'-indoline)-1'-yl)propanamido)-N-hydroxybenzamide; D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D013141:Spiro Compounds; C572590:indoline-2,3-dione; D006655:Histone Deacetylases
keywords: Biological evaluation; HDAC inhibitors; Indoline-2,3-dione derivatives; QSAR; Synthesis