Synthesis and biological evaluation of thiophene-based hydroxamate derivatives as HDACis with antitumor activities
| Autor: | Di Ge, Feifei Yang, Yihua Chen, Hua Zhang, Yang Yang, Han Lina, Na Zhao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Mice
Nude Antineoplastic Agents Thiophenes Hydroxamic Acids 01 natural sciences Histone Deacetylases Mice Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Amide Drug Discovery medicine Thiophene Animals Humans Structure–activity relationship Cells Cultured Cell Proliferation Biological evaluation Pharmacology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Mammary Neoplasms Experimental Cancer medicine.disease Combinatorial chemistry 0104 chemical sciences Histone Deacetylase Inhibitors 030220 oncology & carcinogenesis Molecular Medicine Female Drug Screening Assays Antitumor |
| Zdroj: | Future Medicinal Chemistry. 12:655-672 |
| ISSN: | 1756-8927 1756-8919 |
| Popis: | Aim: Histone deacetylases (HDACs) are one of the validated targets for cancer treatments. In our previous work, we designed a series of bis-substituted aromatic amide HDAC inhibitors (HDACis), among which compounds 7 and 8 showed promising anticancer effects. However, the low solubilities prevented their subsequent developments. We developed additional thiophene-based hydroxamate HDACis in order to improve their physicochemical properties. Materials & methods: In vitro biological evaluations of these analogs revealed potent antiproliferative and antimigrated activities. More importantly, compound 10h exhibited excellent in vivo antitumor activities in MDA-MB-231 xenograft model mice. Furthermore, 10h showed better anticancer activities and drug-like properties than 7. Results & conclusion: Our results proved that thiophene-based hydroxamate HDACis can serve as a promising framework for developing potential anticancer agents. |
| Databáze: | OpenAIRE |
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