Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors

被引：6
|
作者：
Jaikhan, Pattaporn [1 ]
Buranrat, Benjaporn [1 ,2 ]
Itoh, Yukihiro [1 ]
Chotitumnavee, Jiranan [1 ]
Kurohara, Takashi [1 ]
Suzuki, Takayoshi [1 ,3 ]
机构：
[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Sakyo Ku, 1-5 Shimogamohangi Cho, Kyoto 6060823, Japan
[2] Mahasarakham Univ, Fac Med, Biomed Sci Res Unit, Muang Dist 44000, Maha Sarakham, Thailand
[3] Japan Sci & Technol Agcy JST, CREST, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 10期
关键词：
Small molecule; Drug design; Histone deacetylase; Lysine demethylase; Inhibitor; HISTONE DEMETHYLASES; CANCER; DOMAIN; METHYLATION; MECHANISMS;
D O I：
10.1016/j.bmcl.2019.03.028
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Fe(II)/alpha-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.
引用
收藏
页码：1173 / 1176
页数：4
相关论文
共 50 条
  • [31] Discovery and Evaluation of Novel Inhibitors of Mycobacterium Protein Tyrosine Phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic Acid Scaffold
    He, Yantao
    Xu, Jie
    Yu, Zhi-Hong
    Gunawan, Andrea M.
    Wu, Li
    Wang, Lina
    Zhang, Zhong-Yin
    JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (03) : 832 - 842
  • [32] Discovery of trisubstituted pyrazolines as a novel scaffold for the development of selective phosphodiesterase 5 inhibitors
    Abdel-Halim, Mohammad
    Tinsley, Heather
    Keeton, Adam B.
    Weam, Mohammed
    Atta, Noha H.
    Hammam, Mennatallah A.
    Hefnawy, Amr
    Hartmann, Rolf W.
    Engel, Matthias
    Piazza, Gary A.
    Abadi, Ashraf H.
    BIOORGANIC CHEMISTRY, 2020, 104
  • [33] Identification of novel PI3K inhibitors through a scaffold hopping strategy
    Martinez Gonzalez, Sonia
    Isabel Hernandez, Ana
    Maria Alvarez, Rosa
    Rodriguez, Antonio
    Ramos-Lima, Francisco
    Bischoff, James R.
    Isabel Albarran, Maria
    Cebria, Antonio
    Hernandez-Encinas, Elena
    Garcia-Arocha, Jennifer
    Cebrian, David
    Blanco-Aparicio, Carmen
    Pastor, Joaquin
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (21) : 4794 - 4799
  • [34] Extending the use of tadalafil scaffold: Development of novel selective phosphodiesterase 5 inhibitors and histone deacetylase inhibitors
    ElHady, Ahmed K.
    Shih, Shou-Ping
    Chen, Yu-Cheng
    Liu, Yi-Chang
    Ahmed, Nermin S.
    Keeton, Adam B.
    Piazza, Gary A.
    Engel, Matthias
    Abadi, Ashraf H.
    Abdel-Halim, Mohammad
    BIOORGANIC CHEMISTRY, 2020, 98
  • [35] Pyrrole- and indole-containing tranylcypromine derivatives as novel lysine-specific demethylase 1 inhibitors active on cancer cells
    Rodriguez, Veronica
    Valente, Sergio
    Rovida, Stefano
    Rotili, Dante
    Stazi, Giulia
    Lucidi, Alessia
    Ciossani, Giuseppe
    Mattevi, Andrea
    Botrugno, Oronza A.
    Dessanti, Paola
    Mercurio, Ciro
    Vianello, Paola
    Minucci, Saverio
    Varasi, Mario
    Mai, Antonello
    MEDCHEMCOMM, 2015, 6 (04) : 665 - 670
  • [36] Identification of potent and selective HIV-RNase H inhibitors and HIV-integrase inhibitors using an N-hydroxy naphthyridinone scaffold
    Kim, Boyoung
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
  • [37] BACE-1 inhibitors Part 1: Identification of novel hydroxy ethylamines (HEAs)
    Clarke, Brian
    Demont, Emmanuel
    Dingwall, Colin
    Dunsdon, Rachel
    Faller, Andrew
    Hawkins, Julie
    Hussain, Ishrut
    MacPherson, David
    Maile, Graham
    Matico, Rosalie
    Milner, Peter
    Mosley, Julie
    Naylor, Alan
    O'Brien, Alistair
    Redshaw, Sally
    Riddell, David
    Rowland, Paul
    Soleil, Virgime
    Smith, Kathrine J.
    Stanway, Steven
    Stemp, Geoffrey
    Sweitzer, Sharon
    Theobald, Pam
    Vesey, David
    Walter, Daryl S.
    Ward, John
    Wayne, Gareth
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (03) : 1011 - 1016
  • [38] Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
    Boggu, Pulla Reddy
    Venkateswararao, Eeda
    Manickam, Manoj
    Sharma, Niti
    Kang, Jong Seong
    Jung, Sang-Hun
    BIOORGANIC & MEDICINAL CHEMISTRY, 2020, 28 (22)
  • [39] MEDI 32-Optimization of the pyridopyrazinone scaffold as novel inhibitors of PDE5
    Walker, John K.
    Jacobsen, E. J.
    Hughes, Robert O.
    Fobian, Yvette M.
    Brown, David L.
    Heasley, Steven E.
    Owen, Dafydd
    Freskos, John
    Mischke, Brent V.
    Molyneaux, John
    Tollefson, Michael B.
    Blevis-Bal, Radhika
    Brown, David G.
    Moon, Joseph B.
    Phillips, Christopher
    Rogier, Joseph D.
    Maddux, Todd
    Benson, Alan
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2008, 236
  • [40] Identification of novel CK2 inhibitors with a benzofuran scaffold by novel non-radiometric in vitro assays
    Gratz, Andreas
    Kucklaender, Uwe
    Bollig, Ricardo
    Goetz, Claudia
    Jose, Joachim
    MOLECULAR AND CELLULAR BIOCHEMISTRY, 2011, 356 (1-2) : 83 - 90
12345