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

  • Eur J Med Chem. 2013 Jul:65:323-36. doi: 10.1016/j.ejmech.2013.04.062.
Gai-Zhi Liu  1 ,  Hai-Wei Xu ,  Peng Wang ,  Zong-Tao Lin ,  Ying-Chao Duan ,  Jia-Xin Zheng ,  Hong-Min Liu
Affiliations
  • 1. School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450046, PR China. [email protected]
PMID: 23735281 DOI: 10.1016/j.ejmech.2013.04.062
Abstract

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.

Keywords
5-Substituted-3,4-diphenylfuran-2-one; Anti-proliferative; Cell cycle arrest; Prostate cancer; Rofecoxib.