Prochelator BHAPI protects cells against paraquat-induced damage by ROS-triggered iron chelation

作者：Kielar Filip; Helsel Marian E; Wang Qin; Franz Katherine J^*

来源：Metallomics, 2012, 4(9): 899-909.

DOI：10.1039/c2mt20069d

A prochelator named BHAPI (N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyloxy) phenyl) ethylidene) isonicotinohydrazide) based on the structure of experimental metal chelator HAPI (N'-[ 1-(2-hydroxyphenyl) ethyliden] isonicotinoylhydrazide) has been synthesized. The prochelator, which shows limited affinity for metal ions, is converted efficiently upon reaction with hydrogen peroxide into its chelator form, which binds di- and trivalent metal ions, including Zn2+, Cu2+ and Fe3+. This work shows that the prochelator has a protective effect on cells under oxidative stress induced by either hydrogen peroxide or the cytotoxic herbicide paraquat. The effect of BHAPI and HAPI on cellular iron status was assessed by monitoring the mRNA level of the transferrin receptor. Whereas the chelator HAPI induces iron deficiency in cultured retinal pigment epithelial cells, the prochelator does not, providing evidence that the differential metal-binding capacity of these compounds observed in vitro is replicated in the cellular context.

• 出版日期2012