4-Indolyl-N-hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo

Samir Mehndiratta, Ruei Shian Wang, Han Li Huang, Chih Jou Su, Chia Ming Hsu, Yi Wen Wu, Shiow Lin Pan, Jing Ping Liou

研究成果: 雜誌貢獻文章同行評審

23 引文 斯高帕斯(Scopus)


A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC50 1.28 nM and 1.34 nM) and HDAC 2 (IC50 0.90 and 0.53 nM). N-Hydroxy-3-{4-[2-(1H-indol-4-yl)-ethylsulfamoyl]-phenyl}-acrylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI50 of 0.14, 0.25, 0.32, and 0.24 μM, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62.2%. Immunohistochemistry of protein expressions, in PC-3 xenograft model indicated elevated acetyl-histone 3 and prominently inhibited HDAC2 protein expressions. Therefore, compound 13 could be a suitable lead for further investigation and the development of selective HDAC 2 inhibitors as potent anti-cancer compounds.
頁(從 - 到)13-23
期刊European Journal of Medicinal Chemistry
出版狀態已發佈 - 7月 7 2017

ASJC Scopus subject areas

  • 藥理
  • 藥物發現
  • 有機化學


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