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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.

SUBMITTER: Zeng X

PROVIDER: S-EPMC7386434 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Total synthesis and biological evaluation of largazole and derivatives with promising selectivity for cancers cells.

Zeng Xin X Yin Biaolin B Hu Zheng Z Liao Chenzhong C Liu Jinglei J Li Shang S Li Zheng Z Nicklaus Marc C MC Zhou Guangbiao G Jiang Sheng S

Organic letters 20100301 6

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 towa ...[more]

PMID: 20184338

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