Design, synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

Abstract

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17, and 20 exhibited strong cytotoxic activities against the tested cancer cell lines (IC 50 <3 μmol/L). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.

A comparative study of the crystal structures of 2-(4-(2-(4-(3-chlorophenyl)pipera -zinyl)ethyl) benzyl)isoindoline-1,3-dione by synchrotron radiation X-ray powder diffraction and single-crystal X-ray diffraction

“…Recently, naftopidil had also proven to arrest the G1 cell cycle phase [9,10] and induce apoptosis in malignant mesothelioma cell lines [11], which could be potentially used as an anticancer drug. Moreover, the arylpiperazine derivative studied in this research possessed an antitumor capability [12].…”

Synthesis and Antitumor Activity of Novel Arylpiperazine Derivatives Containing the Saccharin Moiety

“…The saccharin moiety has been identified as an important molecular component in various classes of α1a adrenergic receptor antagonists [ 16 ], 5HT1a antagonists [ 17 ], human leukocyte elastase (HLE) inhibitors [ 18 , 19 , 20 , 21 , 22 ], analgesics [ 23 ], human mast cell tryptase inhibitors [ 24 ], and aldehyde dehydrogenase inhibitors [ 25 ]. Moreover, arylpiperazine derivatives have been reported as anticancer drugs for the site-directed chemotherapy of prostate cancer in our previous works [ 26 , 27 , 28 ], and some derivatives have shown significant cytotoxic activity against the tested prostate cancer cell lines. Inspired by these, we herein report the synthesis of a series of novel arylpiperazine derivatives containing the saccharin moiety to identify new anti-prostate cancer drug candidates to treat prostate cancer.…”