摘要
We synthesized a series of pyrimidinedione derivatives and evaluated their activities. The results indicate that compound 6, 4-[5-fluoro-2,6-dioxo-3-(tetrahydro-furan-2-yl)-3,6-dihydro-2H-pyrimidin-1-ylmethyl]-N-hydroxy-benzamide, exhibits potent antiproliferative activity, apoptosis induction with cleavage of caspase and PARP, and enhanced tendency to inhibit HDAC6 (IC50 = 12.4 nM) activity over HDAC1 (IC50 = 1710 nM) and HDAC2 (IC50 = 5500 nM). Compound 6 also inhibits tumor growth and is less toxic than parent 4in vivo. These data provide compelling evidence that compound 6 is a potential antitumor compound with HDAC6 targeted inhibitory activity and may be tested for preclinical investigation for cancer treatment.
原文 | 英語 |
---|---|
頁(從 - 到) | 10226-10235 |
頁數 | 10 |
期刊 | Organic and Biomolecular Chemistry |
卷 | 13 |
發行號 | 40 |
DOIs | |
出版狀態 | 已發佈 - 8月 17 2015 |
ASJC Scopus subject areas
- 生物化學
- 物理與理論化學
- 有機化學