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.

Graphical abstractInhibition of tumor growth by compound 11 in human prostate PC-3 xenograft model.Figure optionsDownload full-size imageDownload as PowerPoint slide