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

9 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)13-23
頁數11
期刊European Journal of Medicinal Chemistry
134
DOIs
出版狀態已發佈 - 七月 7 2017

指紋

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

引用此文

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.

於: European Journal of Medicinal Chemistry, 卷 134, 07.07.2017, p. 13-23.

研究成果: 雜誌貢獻文章

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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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author = "Samir Mehndiratta and Wang, {Ruei Shian} and Huang, {Han Li} and Su, {Chih Jou} and Hsu, {Chia Ming} and Wu, {Yi Wen} and Pan, {Shiow Lin} and Liou, {Jing Ping}",
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AU - Mehndiratta, Samir

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AU - Huang, Han Li

AU - Su, Chih Jou

AU - Hsu, Chia Ming

AU - Wu, Yi Wen

AU - Pan, Shiow Lin

AU - Liou, Jing Ping

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