title: Synthesis and biological evaluation of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles as potent histone deacetylase inhibitors with antitumor activity in vivo.
abstract: A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI(50) values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC(50) values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei 11031, Taiwan.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Huang
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Peng
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Po-Hsien
authors.initials: PH
authors.lastname: Huang
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.forename: Hsun-Yueh
authors.initials: HY
authors.lastname: Chuang
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: C573556:3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles