- Amides of xanthurenic acid as zinc-dependent inhibitors of Lp-PLA(2).
Amides of xanthurenic acid as zinc-dependent inhibitors of Lp-PLA(2).
Bioorganic & medicinal chemistry letters (2012-01-06)
Emme C K Lin, Yi Hu, Christopher M Amantea, Lan M Pham, Julia Cajica, Eric Okerberg, Heidi E Brown, Allister Fraser, Lingling Du, Yasushi Kohno, Junichi Ishiyama, John W Kozarich, Kevin R Shreder
PMID22217870
摘要
AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+) 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.