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

Xianlin Li; Zhenchao Tu; Hua Li; Chunping Liu; Zheng Li; Qiao Sun; Yiwu Yao; Jinsong Liu; Sheng Jiang

doi:10.1021/ml300371t

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

Xianlin Li, Zhenchao Tu, Hua Li, Chunping Liu, Zheng Li, Qiao Sun, Yiwu Yao, Jinsong Liu, Sheng Jiang

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English (US)
Pages (from-to)	132-136
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	1
DOIs	https://doi.org/10.1021/ml300371t
State	Published - Jan 10 2013

Keywords

click chemistry
HDAC inhibitor
largazole
macrocycles
peptides

ASJC Scopus subject areas

Organic Chemistry
Drug Discovery
Biochemistry

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10.1021/ml300371t

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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.",

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author = "Xianlin Li and Zhenchao Tu and Hua Li and Chunping Liu and Zheng Li and Qiao Sun and Yiwu Yao and Jinsong Liu and Sheng Jiang",

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T1 - Biological evaluation of new largazole analogues

T2 - Alteration of macrocyclic scaffold with click chemistry

AU - Li, Xianlin

AU - Tu, Zhenchao

AU - Li, Hua

AU - Liu, Chunping

AU - Li, Zheng

AU - Sun, Qiao

AU - Yao, Yiwu

AU - Liu, Jinsong

AU - Jiang, Sheng

PY - 2013/1/10

Y1 - 2013/1/10

N2 - 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.

AB - 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.

KW - click chemistry

KW - HDAC inhibitor

KW - largazole

KW - macrocycles

KW - peptides

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

Abstract

Keywords

ASJC Scopus subject areas

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