title: Synthesis and activity of largazole analogues with linker and macrocycle modification.
abstract: To characterize largazole's structural requirements for histone deacetylase (HDAC) inhibitory and antiproliferative activities, a series of analogues with modifications to the side chain or 16-membered macrocycle were prepared and biologically evaluated. Structure-activity relationships suggested that the four-atom linker between the macrocycle and octanoyl group in the side chain and the (S)-configuration at the C17 position are critical to repression of HDAC activity. However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity.
authors.affiliation: Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Ying
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Liu
authors.forename: Seong Rim
authors.initials: SR
authors.lastname: Byeon
authors.forename: Hyoungsu
authors.initials: H
authors.lastname: Kim
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luesch
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D013844:Thiazoles; C527895:largazole