期刊
MOLECULES
卷 22, 期 1, 页码 -出版社
MDPI AG
DOI: 10.3390/molecules22010045
关键词
soluble epoxide hydrolase; 5-lipoxygenase; inflammation; designed multitarget ligands; leukocyte-endothelial cell interaction
资金
- Deutsche Forschungsgemeinschaft (DFG) [Sachbeihilfe PR1405/2-2, SFB 1039]
- German Cancer Consortium (DKTK)
The arachidonic acid cascade is a key player in inflammation, and numerous well-established drugs interfere with this pathway. Previous studies have suggested that simultaneous inhibition of 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH) results in synergistic anti-inflammatory effects. In this study, a novel prototype of a dual 5-LO/sEH inhibitor KM55 was rationally designed and synthesized. KM55 was evaluated in enzyme activity assays with recombinant enzymes. Furthermore, activity of KM55 in human whole blood and endothelial cells was investigated. KM55 potently inhibited both enzymes in vitro and attenuated the formation of leukotrienes in human whole blood. KM55 was also tested in a cell function-based assay. The compound significantly inhibited the LPS-induced adhesion of leukocytes to endothelial cells by blocking leukocyte activation.
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