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PXD 101 analogs with L ‐phenylglycine‐containing branched cap as histone deacetylase inhibitors
Author(s) -
Li Jingyao,
Li Xiaoyang,
Wang Xue,
Hou Jinning,
Zang Jie,
Gao Shuai,
Xu Wenfang,
Zhang Yingjie
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12787
Subject(s) - histone deacetylase , chemistry , histone , gene isoform , in vitro , stereochemistry , biochemistry , dna , gene
Histone deacetylases ( HDAC s) allow histones to wrap DNA more tightly and finally lead to the repression of some tumor suppressor genes. Histone deacetylase inhibitors ( HDACI s) have been proved to have effects on tumorigenesis and tumor progression. In this study, we reported the design, synthesis, and in vitro activity evaluation of novel PXD 101 analogs with L ‐phenylglycine‐containing cap as HDACI s. Our results showed that HDAC s inhibitory activities of compounds 10k , 10r , and 10s were not only superior to the first approved HDACI SAHA , but also comparable to their parent compound PXD 101, a recently approved HDACI in 2014. However, all 6 selected PXD 101 analogs exhibited moderate in vitro antiproliferative activities, less potent than PXD 101 and SAHA . Representative compound 10s showed similar HDAC s isoform selective profile to PXD 101, which demonstrated that introduction of L ‐phenylglycine‐containing branched cap group could not change the isoform selectivity of PXD 101 dramatically.