title: 4-Indolyl-N-hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo.
abstract: A series of 4,5-indolyl-N-hydroxyphenylacrylamides, as HDAC inhibitors, has been synthesized and evaluated in vitro and in vivo. 4-Indolyl compounds 13 and 17 functions as potent inhibitors of HDAC1 (IC501.28 nM and 1.34 nM) and HDAC 2 (IC500.90 and 0.53 nM). N-Hydroxy-3-{4-[2-(1H-indol-4-yl)-ethylsulfamoyl]-phenyl}-acrylamide (13) inhibited the human cancer cell growth of PC3, A549, MDA-MB-231 and AsPC-1 with a GI50of 0.14, 0.25, 0.32, and 0.24 μM, respectively. In in vivo evaluations bearing prostate PC3 xenografts nude mice model, compound 13 suppressed tumor growth with a tumor growth inhibition (TGI) of 62.2%. Immunohistochemistry of protein expressions, in PC-3 xenograft model indicated elevated acetyl-histone 3 and prominently inhibited HDAC2 protein expressions. Therefore, compound 13 could be a suitable lead for further investigation and the development of selective HDAC 2 inhibitors as potent anti-cancer compounds.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University (TMU), Taiwan.
authors.forename: Samir
authors.initials: S
authors.lastname: Mehndiratta
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taiwan.
authors.forename: Ruei-Shian
authors.initials: RS
authors.lastname: Wang
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan.
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Huang
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan.
authors.forename: Chih-Jou
authors.initials: CJ
authors.lastname: Su
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Wu
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, TMU, Taiwan; Department of Pharmacology, College of Medicine, Taipei Medical University, Taiwan.
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University (TMU), Taiwan. Electronic address: jpl@tmu.edu.tw.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000178:Acrylamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D007211:Indoles; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: Acrylamide; Cancer; HDAC; Hydroxamic acid; Indole; Prostate cancer