16 Citations (Scopus)

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

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Keywords

  • Histone deacetylase inhibitors
  • Prostate cancer
  • Quinoline

ASJC Scopus subject areas

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

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