title: Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors.
abstract: A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48 μM, respectively.
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Chengqing
authors.initials: C
authors.lastname: Ning
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Bi
authors.forename: Yujun
authors.initials: Y
authors.lastname: He
authors.forename: WenYuan
authors.initials: W
authors.lastname: Huang
authors.forename: Lifei
authors.initials: L
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Sihan
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.forename: Niefang
authors.initials: N
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D061986:MCF-7 Cells; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C029010:cinnamic acid; D014508:Urea; D013890:Thiourea
keywords: Cinnamic hydroxamaic acid; HDAC; Histone deacetylase; Thiourea; Urea