title: Total synthesis and biological evaluation of largazole and derivatives with promising selectivity for cancers cells.
abstract: The efficient total synthesis of the natural substance largazole is described. Using this strategy, a small library of largazole analogs was developed. Structure-activity relationship studies suggested that the geometry of the alkene in the side chain is critical. While the largazole's analogues with trans-alkene are potent for the antiproliferative effect, those with cis-alkene are completely inactive. Most importantly, replacement of valine with tyrosine in largazole increased selectivity toward human cancer cells over human normal cells more than 100-fold.
authors.affiliation: Guangzhou Institute of Biomedicine and Health, CAS, Guangzhou 510663, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Biaolin
authors.initials: B
authors.lastname: Yin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Chenzhong
authors.initials: C
authors.lastname: Liao
authors.forename: Jinglei
authors.initials: J
authors.lastname: Liu
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Marc C
authors.initials: MC
authors.lastname: Nicklaus
authors.forename: Guangbiao
authors.initials: G
authors.lastname: Zhou
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D013844:Thiazoles; C527895:largazole