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

…, J Lyle, PM Loadman, SJ Crabb, G Packham…

文献索引：Benelkebir, Hanae; Marie, Sabrina; Hayden, Annette L.; Lyle, Jason; Loadman, Paul M.; Crabb, Simon J.; Packham, Graham; Ganesan Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 12 p. 3650 - 3658

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被引用次数: 37

摘要

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⩽ 5min) to the thiol which has a half-life of 51min.