Amides of xanthurenic acid as zinc-dependent inhibitors of Lp-PLA2
| Autor: | Eric Okerberg, Julia Cajica, Kevin R. Shreder, Yasushi Kohno, Lan M. Pham, Heidi E. Brown, Junichi Ishiyama, Yi Hu, John W. Kozarich, Allister Fraser, Lingling Du, Emme C.K. Lin, Christopher M. Amantea |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Xanthurenates
Stereochemistry Clinical Biochemistry Pharmaceutical Science chemistry.chemical_element Zinc Biochemistry Metal Structure-Activity Relationship chemistry.chemical_compound Amide Drug Discovery Organometallic Compounds Xanthurenic acid Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Amides Enzyme visual_art 1-Alkyl-2-acetylglycerophosphocholine Esterase visual_art.visual_art_medium Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:868-871 |
| ISSN: | 0960-894X |
| Popis: | AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100 nM inhibitor of Lp-PLA2. However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA2 did not change. Subsequent metal screening experiments determined the inhibition to be Zn2+ dependent. Structure–activity relationship studies indicated the presence of the 4-hydroxy group to be critical and selected substituted phenyl, polycyclic, and cycloaliphatic amides of xanthurenic acid to be well tolerated. |
| Databáze: | OpenAIRE |
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