Design, synthesis, and biological evaluation of largazole derivatives: alteration of the zinc-binding domain

A new series of largazole analogues in which the side chain was replaced with disulfide groups were synthesized, and their biological activities were evaluated. Compound 8 bearing an octyl moiety showed much better selectivity for HDAC1 over HDAC7 than largazole (320-fold). Structure–activity relati...

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Bibliographic Details
Published in:Tetrahedron 2014-10, Vol.70 (42), p.7763-7769
Main Authors: Su, Jinyue, Qiu, Yatao, Ma, Kun, Yao, Yiwu, Wang, Zhen, Li, Xianling, Zhang, Dayong, Tu, Zhengchao, Jiang, Sheng
Format: Article
Language:English
Subjects:
Disulfide bridge
HDAC inhibitor
largazole
Macrocycles
Peptides
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Summary:A new series of largazole analogues in which the side chain was replaced with disulfide groups were synthesized, and their biological activities were evaluated. Compound 8 bearing an octyl moiety showed much better selectivity for HDAC1 over HDAC7 than largazole (320-fold). Structure–activity relationships suggested that the length in the disulfide chain of largazole is important for the selectivity toward HDAC1 over HDAC7. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2014.05.078