Potent and Orally Efficacious Bisthiazole-Based Histone Deacetylase Inhibitors

被引：31
作者：
Chen, Fei [1 ]
Chai, Hui [1 ]
Su, Ming-Bo [1 ]
Zhang, Yang-Ming [1 ]
Li, Jia [1 ]
Xie, Xin [1 ]
Nan, Fa-Jun [1 ]
机构：
[1] Shanghai Inst Mat Med, Chinese Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2014年 / 5卷 / 06期
基金：
中国国家自然科学基金;
关键词：
Histone deacetylase inhibitors; largazole; bisthiazole; CONCISE TOTAL-SYNTHESIS; HDAC INHIBITORS; BIOLOGICAL EVALUATION; LARGAZOLE ANALOGS; TRICHOSTATIN-A; DERIVATIVES; SAHA; INDUCTION; MECHANISM; APOPTOSIS;
D O I：
10.1021/ml400470s
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Inspired by the thiazole thiazoline cap group in natural product largazole, a series of structurally simplified bisthiazole-based histone deacetylase inhibitors were prepared and evaluated. Compound 8f was evaluated in vivo in an experimental autoimmune encephalomyelitis (EAE) model and found to be orally efficacious in ameliorating clinical symptoms of EAE mice.
引用
收藏
页码：628 / 633
页数：6
相关论文
共 55 条
  • [1] HDAC inhibitors as anti-inflammatory agents
    Adcock, I. M.
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2007, 150 (07) : 829 - 831
  • [2] Total synthesis of largazole and analogues: HDAC inhibition, antiproliferative activity and metabolic stability
    Benelkebir, Hanae
    Marie, Sabrina
    Hayden, Annette L.
    Lyle, Jason
    Loadman, Paul M.
    Crabb, Simon J.
    Packham, Graham
    Ganesan, A.
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (12) : 3650 - 3658
  • [3] Largazole and Analogues with Modified Metal-Binding Motifs Targeting Histone Deacetylases: Synthesis and Biological Evaluation
    Bhansali, Pravin
    Hanigan, Christin L.
    Casero, Robert A., Jr.
    Tillekeratne, L. M. Viranga
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (21) : 7453 - 7463
  • [4] Anticancer activities of histone deacetylase inhibitors
    Bolden, Jessica E.
    Peart, Melissa J.
    Johnstone, Ricky W.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) : 769 - 784
  • [5] Total synthesis and biological mode of action of largazole: A potent Class I histone deacetylase inhibitor
    Bowers, Albert
    West, Nathan
    Taunton, Jack
    Schreiber, Stuart L.
    Bradner, James E.
    Williams, Robert M.
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (33) : 11219 - 11222
  • [6] Synthesis and Conformation-Activity Relationships of the Peptide Isosteres of FK228 and Largazole
    Bowers, Albert A.
    Greshock, Thomas J.
    West, Nathan
    Estiu, Guillermina
    Schreiber, Stuart L.
    Wiest, Olaf
    Williams, Robert M.
    Bradner, James E.
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (08) : 2900 - 2905
  • [7] Synthesis and Histone Deacetylase Inhibitory Activity of Largazole Analogs: Alteration of the Zinc-Binding Domain and Macrocyclic Scaffold
    Bowers, Albert A.
    West, Nathan
    Newkirk, Tenaya L.
    Troutman-Youngman, Annie E.
    Schreiber, Stuart L.
    Wiest, Olaf
    Bradner, James E.
    Williams, Robert M.
    [J]. ORGANIC LETTERS, 2009, 11 (06) : 1301 - 1304
  • [8] Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitis
    Camelo, S
    Iglesias, AH
    Hwang, D
    Due, B
    Ryu, H
    Smith, K
    Gray, SG
    Imitola, J
    Duran, G
    Assaf, B
    Langley, B
    Khoury, SJ
    Stephanopoulos, G
    De Girolami, U
    Ratan, RR
    Ferrante, RJ
    Dangond, F
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2005, 164 (1-2) : 10 - 21
  • [9] ROMIDEPSIN FOR THE TREATMENT OF CUTANEOUS T-CELL LYMPHOMA
    Campas-Moya, Clara
    [J]. DRUGS OF TODAY, 2009, 45 (11) : 787 - 795
  • [10] Synthesis and Biological Evaluation of C7-Demethyl Largazole Analogues
    Chen, Fei
    Gao, An-Hui
    Li, Jia
    Nan, Fa-Jun
    [J]. CHEMMEDCHEM, 2009, 4 (08) : 1269 - 1272
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