Abstract

This study describes the development of a series of 1-arylsulfonyl-6-(N-hydroxyacrylamide)tetrahydroquinolines, potent histone deacetylase (HDAC) inhibitors which are cytotoxic to PC-3 cells. (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (11) exhibits marked anti-HDAC and antiproliferative activity, and is slightly more effective than N1-hydroxy-N8-phenyloctanediamide (SAHA, Vorinostat, 1). In a xenograft tumor model, 11, at doses of 100 or 200 mg/kg orally, suppresses the growth of PC-3 cells and leads to tumor growth inhibition of 38.8% and 57.9%, respectively. Compound 11 is a lead compound for further development of potential prostate cancer inhibitors.

Original languageEnglish
Pages (from-to)320-330
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume89
DOIs
Publication statusPublished - 2015

Fingerprint

Histone Deacetylase Inhibitors
Tumors
Prostatic Neoplasms
Cells
Lead compounds
Histone Deacetylases
Acrylamide
Growth
Heterografts
Neoplasms
1,2,3,4-tetrahydroquinoline
vorinostat
Lead

Keywords

  • Histone deacetylase inhibitors
  • Prostate cancer
  • Quinoline

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

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title = "1-arylsulfonyl-5-(N-hydroxyacrylamide)tetrahydroquinolines as potent histone deacetylase inhibitors suppressing the growth of prostate cancer cells",
abstract = "This study describes the development of a series of 1-arylsulfonyl-6-(N-hydroxyacrylamide)tetrahydroquinolines, potent histone deacetylase (HDAC) inhibitors which are cytotoxic to PC-3 cells. (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (11) exhibits marked anti-HDAC and antiproliferative activity, and is slightly more effective than N1-hydroxy-N8-phenyloctanediamide (SAHA, Vorinostat, 1). In a xenograft tumor model, 11, at doses of 100 or 200 mg/kg orally, suppresses the growth of PC-3 cells and leads to tumor growth inhibition of 38.8{\%} and 57.9{\%}, respectively. Compound 11 is a lead compound for further development of potential prostate cancer inhibitors.",
keywords = "Histone deacetylase inhibitors, Prostate cancer, Quinoline",
author = "Yi-Min Liu and Lee, {Hsueh Yun} and Chun-Han Chen and Chia-Hua Lee and Li-Ting Wang and Pan, {Shiow Lin} and Mei-Jung Lai and Teng-Kuang Yeh and Liou, {Jing Ping}",
year = "2015",
doi = "10.1016/j.ejmech.2014.10.052",
language = "English",
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journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
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T1 - 1-arylsulfonyl-5-(N-hydroxyacrylamide)tetrahydroquinolines as potent histone deacetylase inhibitors suppressing the growth of prostate cancer cells

AU - Liu, Yi-Min

AU - Lee, Hsueh Yun

AU - Chen, Chun-Han

AU - Lee, Chia-Hua

AU - Wang, Li-Ting

AU - Pan, Shiow Lin

AU - Lai, Mei-Jung

AU - Yeh, Teng-Kuang

AU - Liou, Jing Ping

PY - 2015

Y1 - 2015

N2 - This study describes the development of a series of 1-arylsulfonyl-6-(N-hydroxyacrylamide)tetrahydroquinolines, potent histone deacetylase (HDAC) inhibitors which are cytotoxic to PC-3 cells. (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (11) exhibits marked anti-HDAC and antiproliferative activity, and is slightly more effective than N1-hydroxy-N8-phenyloctanediamide (SAHA, Vorinostat, 1). In a xenograft tumor model, 11, at doses of 100 or 200 mg/kg orally, suppresses the growth of PC-3 cells and leads to tumor growth inhibition of 38.8% and 57.9%, respectively. Compound 11 is a lead compound for further development of potential prostate cancer inhibitors.

AB - This study describes the development of a series of 1-arylsulfonyl-6-(N-hydroxyacrylamide)tetrahydroquinolines, potent histone deacetylase (HDAC) inhibitors which are cytotoxic to PC-3 cells. (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (11) exhibits marked anti-HDAC and antiproliferative activity, and is slightly more effective than N1-hydroxy-N8-phenyloctanediamide (SAHA, Vorinostat, 1). In a xenograft tumor model, 11, at doses of 100 or 200 mg/kg orally, suppresses the growth of PC-3 cells and leads to tumor growth inhibition of 38.8% and 57.9%, respectively. Compound 11 is a lead compound for further development of potential prostate cancer inhibitors.

KW - Histone deacetylase inhibitors

KW - Prostate cancer

KW - Quinoline

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