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

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.