A Series of Novel HDAC Inhibitors with Anthraquinone as a Cap Group
| Autor: | Bin He, Jie Wang, Xiaoxue Chen, Yong-Long Zhao, Ai-Min Wang, Zhuoxian Cao, Yan Li, Jingzi Liu, Yefang Zou, Yan-Qin Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
DNA Repair
medicine.drug_class DNA repair Drug Evaluation Preclinical Anthraquinones 010402 general chemistry 01 natural sciences Anthraquinone Cell Line chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Humans Vorinostat Cell Proliferation biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Cell growth Topoisomerase Histone deacetylase inhibitor General Chemistry General Medicine 0104 chemical sciences Histone Deacetylase Inhibitors DNA Topoisomerases Type II Biochemistry Cell culture Drug Design biology.protein Histone deacetylase medicine.drug |
| Zdroj: | Chemicalpharmaceutical bulletin. 68(7) |
| ISSN: | 1347-5223 |
| Popis: | Although anthraquinone derivatives possess significant antitumor activity, most of them also displayed those side effects like cardiotoxicity, mainly owing to their inhibition of topoisomerase II of DNA repair mechanisms. Our raised design strategy by switching therapeutic target from topoisomerase II to histone deacetylase (HDAC) has been applied to the design of anthraquinone derivatives in current study. Consequently, a series of novel HDAC inhibitors with a tricylic diketone of anthraquinone as a cap group have been synthesized. After screening and evaluation, compounds 4b, 4d, 7b and 7d have displayed the comparable inhibition in enzymatic activity and cell proliferation than that of Vorinostat (SAHA). Notably, compound 4b showed certain selectivity of antiproliferative effects on cancer cell lines over non-cancer cell lines. |
| Databáze: | OpenAIRE |
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