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Modular synthesis and biological activity of pyridyl-based analogs of the potent Class I Histone Deacetylase Inhibitor Largazole.

ABSTRACT: The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein.

SUBMITTER: Clausen DJ

PROVIDER: S-EPMC4626217 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Modular synthesis and biological activity of pyridyl-based analogs of the potent Class I Histone Deacetylase Inhibitor Largazole.

Clausen Dane J DJ Smith William B WB Haines Brandon E BE Wiest Olaf O Bradner James E JE Williams Robert M RM

Bioorganic & medicinal chemistry 20150331 15

The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein. ...[more]

PMID: 26054247

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