摘要
A series of phenylurea hydroxamic acids incorporating pharmacophores of inhibitors of HDAC inhibitors and VEGFR-2 has been designed. Most of the compounds show antiproliferative activity comparable to that of Vorinostat and Sorafenib, and better EPC inhibitory activity. Enzymatic assays and Western blotting results indicated that compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A docking study revealed that the polar hydroxamic acid retains the interaction with HDAC through a zinc ion and also interacts with some residues of the active site of VEGFR-2. Despite 14 displaying a weaker VEGFR-2 activity, a possible route to develop potent HDAC/VEGFR-2 inhibitors is suggested.
原文 | 英語 |
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文章編號 | 116454 |
期刊 | Bioorganic and Medicinal Chemistry |
卷 | 50 |
DOIs | |
出版狀態 | 已發佈 - 11月 15 2021 |
ASJC Scopus subject areas
- 生物化學
- 分子醫學
- 分子生物學
- 藥學科學
- 藥物發現
- 臨床生物化學
- 有機化學