Efficient solid-phase synthesis of FK228 analogues as potent antitumoral agents.
Novel structural analogues of a HDAC inhibitor FK228 have been synthesized by modifying the most synthetically challenging unit, (3 S,4 E)-3-hydroxy-7-mercaptoheptenoic acid, with simple isosteric substitutions. These changes did not alter the backbone structure from FK228 but enabled facile and rapid synthesis by using readily available starting materials and high-yielding reactions. FK228 analogues were examined for their antitumoral activity on a variety of human cancer cells and led to the identification of new potent compounds.
Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75080, USA.
Salvatore
S
Di Maro
Rey-Chen
RC
Pong
Jer-Tsong
JT
Hsieh
Jung-Mo
JM
Ahn
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047630:Depsipeptides; C087123:romidepsin