Abstract

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.

Original languageEnglish
Pages (from-to)13-23
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume134
DOIs
Publication statusPublished - Jul 7 2017

Fingerprint

Heterografts
Tumors
Bearings (structural)
Histone Deacetylase Inhibitors
Acrylamide
Cell growth
Histones
Inhibitory Concentration 50
Neoplasms
Proteins
Growth
Nude Mice
Prostate
Immunohistochemistry
Lead

Keywords

  • Acrylamide
  • Cancer
  • HDAC
  • Hydroxamic acid
  • Indole
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

4-Indolyl-N-hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo. / Mehndiratta, Samir; Wang, Ruei Shian; Huang, Han Li; Su, Chih Jou; Hsu, Chia Ming; Wu, Yi Wen; Pan, Shiow Lin; Liou, Jing Ping.

In: European Journal of Medicinal Chemistry, Vol. 134, 07.07.2017, p. 13-23.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Mehndiratta, Samir

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AU - Su, Chih Jou

AU - Hsu, Chia Ming

AU - Wu, Yi Wen

AU - Pan, Shiow Lin

AU - Liou, Jing Ping

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