title: 1-Arylsulfonyl-5-(N-hydroxyacrylamide)tetrahydroquinolines as potent histone deacetylase inhibitors suppressing the growth of prostate cancer cells.
abstract: This study describes the development of a series of 1-arylsulfonyl-6-(N-hydroxyacrylamide)tetrahydroquinolines, potent histone deacetylase (HDAC) inhibitors which are cytotoxic to PC-3 cells. (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (11) exhibits marked anti-HDAC and antiproliferative activity, and is slightly more effective than N(1)-hydroxy-N(8)-phenyloctanediamide (SAHA, Vorinostat, 1). In a xenograft tumor model, 11, at doses of 100 or 200 mg/kg orally, suppresses the growth of PC-3 cells and leads to tumor growth inhibition of 38.8% and 57.9%, respectively. Compound 11 is a lead compound for further development of potential prostate cancer inhibitors.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Wang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: jpl@tmu.edu.tw.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008297:Male; D008819:Mice, Nude; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D015363:Quinolones; D006655:Histone Deacetylases
keywords: Histone deacetylase inhibitors; Prostate cancer; Quinoline