Design, synthesis and biological evaluation of indeno[1,2-d]thiazole derivatives as potent histone deacetylase inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2013-06, Vol.23 (11), p.3200-3203
• Main Authors: Zhou, Ming, Ning, Chengqing, Liu, Ruihuan, He, Yujun, Yu, Niefang
• Format: Article
• Language: English
• Subjects: Binding Sites; Cell Proliferation - drug effects; chemistry; Drug Design; Drug Screening Assays, Antitumor; growth retardation; HCT116 Cells; HDAC; Heterocyclic Compounds, 3-Ring - chemical synthesis; Heterocyclic Compounds, 3-Ring - chemistry; Heterocyclic Compounds, 3-Ring - toxicity; histone deacetylase; Histone Deacetylase Inhibitors - chemical synthesis; Histone Deacetylase Inhibitors - chemistry; Histone Deacetylase Inhibitors - toxicity; Histone deacetylases; Histone Deacetylases - chemistry; Histone Deacetylases - metabolism; Humans; Hydroxamic acids; Hydroxamic Acids - chemical synthesis; Hydroxamic Acids - chemistry; Hydroxamic Acids - toxicity; Indeno[1,2-d]thiazole; inhibitory concentration 50; MCF-7 Cells; Molecular Docking Simulation; Protein Structure, Tertiary; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - toxicity; Tricyclic
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.04.004

Novel indeno[1,2-d]thiazole hydroxamic acids were designed, synthesized, and evaluated for histone deacetylases (HDACs) inhibition and antiproliferative activities on tumor cell lines. Most of the tested compounds exhibited HDAC inhibition and antiproliferative activity against both MCF7 and HCT116 cells with GI50 values in the sub-micromolar range. Among them, compound 6o showed good inhibitory activity against pan-HDAC with IC50 value of 0.14μM and significant growth inhibition on MCF7 and HCT116 cells with GI50 values of 0.869 and 0.535μM, respectively.