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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Jaikhan, Pattaporn¹  Buranrat, Benjaporn^1,2  Itoh, Yukihiro¹  Chotitumnavee, Jiranan¹  Kurohara, Takashi¹  Suzuki, Takayoshi^1,3 

[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

关键词: Small molecule;    Drug design;    Histone deacetylase;    Lysine demethylase;    Inhibitor;   

DOI  :  10.1016/j.bmcl.2019.03.028

来源: Elsevier

【 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.

【 授权许可】

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