Synthesis and biological evaluation of 3-(4-fluorophenyl)-1H-pyrazole derivatives as androgen receptor antagonists.

A novel series of 3-(4-fluorophenyl)-1H-pyrazole derivatives were synthesized and evaluated for their antiproliferative activity against two prostate cancer cell lines (LNCaP and PC-3) and androgen receptor target gene prostate-specific antigen (PSA) inhibitory activity in LNCaP cells. Several compounds showed potent antiproliferative activity against LNCaP cells and showed a promising PSA downregulation rate. Among these, compound 10e selectively inhibited LNCaP cell growth with an IC50 value of 18 μmol/l and showed a PSA downregulation rate of 46%, which was better than the lead compound T3.

Discovery of novel androgen receptor antagonists: a hybrid approach of pharmacophore-based and docking-based virtual screening.

Androgen receptor (AR) is an attractive target for the treatment of prostate cancer. An integrated pharmacophore-based and docking-based virtual screening approach was applied to identify novel AR antagonists with a distinct scaffold. The candidate compounds were evaluated for their abilities to inhibit prostate cancer cell proliferation and AR target gene prostate-specific antigen gene expression as well as the binding affinity to AR.