title: 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.
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Liu
authors.affiliation: The Methodist Hospital Research Institute , Houston, Texas, 77030, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou, 510530, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
keywords: HDAC inhibitor; click chemistry; largazole; macrocycles; peptides