Stereoselective synthesis and anti-proliferative effects on prostate cancer evaluation of 5-substituted-3,4-diphenylfuran-2-ones

•Series of novel 5-substituted-3,4-diphenylfuran-2-ones were synthesized.•Some compounds showed good anti-proliferative effects on prostate cancer.•Compounds 13p exhibited potent anticancer activity with IC50 value was 5 μM.•Compound 13p showed cell cycle arrest at G0/G1 phase and may induced apoptosis.•These compounds are easy to synthesize.

Series of 5-substituted-3,4-diphenylfuran-2-ones were stereoselectively prepared. Their potential anti-proliferative effects on prostate cancer and some of their cyclooxygenases (COXs) inhibitory activities were evaluated. Structure–activity relationship (SAR) data, acquired by substituent modification at the para-position and ortho-position of the C-3 phenyl ring and 5-substituted modification of the central furanone, showed that 3-(2-chloro-phenyl)-4-(4-methanesulfonyl-phenyl)-5-(1-methoxy-ethyl)-5H-furan-2-one (13p) was the most potent compound and could effectively reduce the proliferation of prostate cancer cells (PC3 cell IC50 = 20 μM; PC3 PCDNA cell IC50 = 5 μM; PC3 SKP2 cell IC50 = 5 μM; DU145 cell IC50 = 25 μM). The cell cycle analysis for 13p in DU145 indicated that 13p may induce G1 phase arrest.

Graphical abstractThe most potent compound 13p showed good anti-proliferative effects on prostate cancer (IC50 = 5 μM). The cell cycle analysis for 13p in DU145 indicated that 13p may induce G1 arrest.Figure optionsDownload full-size imageDownload as PowerPoint slide