Total synthesis of largazole and analogues: HDAC inhibition, antiproliferative activity and metabolic stability

Hanae Benelkebir, Sabrina Marie, Annette L. Hayden, Jason Lyle, Paul M. Loadman, Simon J. Crabb, Graham Packham, A Ganesan

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50 Citations (Scopus)

Abstract

The total synthesis of largazole and four analogues is reported. All analogues were nanomolar HDAC inhibitors. The antiproliferative activity is driven by lipophilicity and cell permeability. In murine liver homogenates, largazole is rapidly metabolized (half-life ?5 min) to the thiol which has a half-life of 51 min.
Original languageEnglish
Pages (from-to)3650-3658
Number of pages9
JournalBioorganic & Medicinal Chemistry
Volume19
Issue number12
DOIs
Publication statusPublished - 15 Jun 2011

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