2-(Phenylsulfonyl)quinoline N -hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase
| Autor: | Hsueh Yun Lee, Ting Yi Sung, Jing Ping Liou, Chia-Ron Yang, Sunil Kumar, Chih Jou Su, Chih Yi Chang, Yuh Hsuan Chao, Chia Ming Hsu, Yi Zhen Huang, Samir Mehndiratta, Yu Hsuan Li, Han Li Huang |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Stereochemistry Antineoplastic Agents Apoptosis 01 natural sciences Histone Deacetylases Histones Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Histone H3 0302 clinical medicine Tubulin Cell Line Tumor Drug Discovery Animals Humans Moiety Cell Proliferation Pharmacology A549 cell Sulfonyl chemistry.chemical_classification 010405 organic chemistry Organic Chemistry Quinoline General Medicine Xenograft Model Antitumor Assays 0104 chemical sciences Histone Deacetylase Inhibitors chemistry Acetylation 030220 oncology & carcinogenesis Quinolines Histone deacetylase Linker |
| Zdroj: | European Journal of Medicinal Chemistry. 122:92-101 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2016.06.023 |
| Popis: | This study reports the design and synthesis of 2-(phenylsulfonyl)quinoline N-hydroxyacrylamides (8a–k). Structure-activity relationship studies focusing on regio-effect of N-hydroxyacrylamide moiety and influence of the sulfonyl linker revealed that N-hydroxy-3-[3-(quinoline-2-sulfonyl)-phenyl]-acrylamide (8f) showed remarkable enzymatic and cellular activity. The GI50 values of 8f for HL-60, HCT116, PC-3, and A549 cells were found to be 0.29, 0.08, 0.15, and 0.27 μM, respectively. The compounds are therefore more potent than FDA approved PXD-101 and SAHA. They also have an effect on the acetylation degree of histone H3 and α-tubulin. In in vivo studies, 8f showed marked inhibition of the growth of HCT116 xenografts. |
| Databáze: | OpenAIRE |
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