Synthesis and activity of largazole analogues with linker and macrocycle modification.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ying, Y; Liu, Y; Byeon, SR; Kim, H; Luesch, H; Hong, J

Published Date

  • September 2008

Published In

Volume / Issue

  • 10 / 18

Start / End Page

  • 4021 - 4024

PubMed ID

  • 18707106

Pubmed Central ID

  • 18707106

Electronic International Standard Serial Number (EISSN)

  • 1523-7052

International Standard Serial Number (ISSN)

  • 1523-7060

Digital Object Identifier (DOI)

  • 10.1021/ol801532s


  • eng