title: Stereoselective synthesis and anti-proliferative effects on prostate cancer evaluation of 5-substituted-3,4-diphenylfuran-2-ones.
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.
authors.affiliation: School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450046, PR China. liugaizhi@126.com
authors.forename: Gai-Zhi
authors.initials: GZ
authors.lastname: Liu
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Lin
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Duan
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Zheng
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C586283:3,4-diphenylfuran-2-one; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: 5-Substituted-3,4-diphenylfuran-2-one; Anti-proliferative; Cell cycle arrest; Prostate cancer; Rofecoxib