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Biological evaluation of new largazole analogues: alteration of macrocyclic scaffold with click chemistry.

ABSTRACT: We report the design, synthesis, and biological evaluation of a new series of largazole analogues in which a 4-methylthiazoline moiety was replaced with a triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring was identified to show much better selectivity for HDAC1 over HDAC9 than largazole (10-fold). This work could serve as a foundation for further exploration of selective HDAC inhibitors using a largazole molecular scaffold.

SUBMITTER: Li X

PROVIDER: S-EPMC4027506 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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Biological evaluation of new largazole analogues: alteration of macrocyclic scaffold with click chemistry.

Li Xianlin X Tu Zhenchao Z Li Hua H Liu Chunping C Li Zheng Z Sun Qiao Q Yao Yiwu Y Liu Jinsong J Jiang Sheng S

ACS medicinal chemistry letters 20121205 1

We report the design, synthesis, and biological evaluation of a new series of largazole analogues in which a 4-methylthiazoline moiety was replaced with a triazole and tetrazole ring, respectively. Compound 7 bearing a tetrazole ring was identified to show much better selectivity for HDAC1 over HDAC9 than largazole (10-fold). This work could serve as a foundation for further exploration of selective HDAC inhibitors using a largazole molecular scaffold. ...[more]

PMID: 24900575

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