Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap
| Autor: | Pannan Miao, Jiahui Lv, Feng He, Jingde Wu, Ana Xu, Qiuqiong Zhang, Chenggong Yu, Xiangna Zhang, Ying Qu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Antineoplastic Agents Biochemistry Histone Deacetylases Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Drug Discovery Humans Protein Isoforms Moiety Molecular Biology Cell Proliferation Indole test Binding Sites Chemistry Organic Chemistry Small molecule Histone Deacetylase Inhibitors Molecular Docking Simulation 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Benzamides Molecular Medicine Histone deacetylase Selectivity Linker HeLa Cells |
| Zdroj: | Bioorganic & Medicinal Chemistry. 26:1859-1868 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2018.02.033 |
| Popis: | Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N -hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N -hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o , 4p , 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA. |
| Databáze: | OpenAIRE |
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