title: Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents.
abstract: Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.
authors.affiliation: Shanghai Huilun Life Sciences & Technology Co. Ltd, Shanghai 201108, China. Electronic address: chengjianjun83@163.com.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Shanghai Huilun Life Sciences & Technology Co. Ltd, Shanghai 201108, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Shanghai Huilun Life Sciences & Technology Co. Ltd, Shanghai 201108, China.
authors.forename: Sihua
authors.initials: S
authors.lastname: Guo
authors.affiliation: Shanghai Huilun Life Sciences & Technology Co. Ltd, Shanghai 201108, China.
authors.forename: Hangdeng
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Shanghai Huilun Life Sciences & Technology Co. Ltd, Shanghai 201108, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: Antitumor; Histone deacetylases; Hydroxamate; Vorinostat