1-Arylsulfonyl-5-(N-hydroxyacrylamide)tetrahydroquinolines as potent histone deacetylase inhibitors suppressing the growth of prostate cancer cells

• A new series of HDAC inhibitors with tetrahydroquinolines core have been designed and synthesized.
• This series of compounds tend to inhibit the growth of prostate cancer cells.
• Compound 11 exhibited potent in vitro and in vivo anti-prostate cancer activity.

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.

Inhibition of tumor growth by compound 11 in human prostate PC-3 xenograft model.Figure optionsDownload as PowerPoint slide