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

Journal Article (Journal Article)

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 Zn(2+), Cu(2+) and Fe(3+). 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.

Full Text

Duke Authors

Cited Authors

  • Kielar, F; Helsel, ME; Wang, Q; Franz, KJ

Published Date

  • August 2012

Published In

Volume / Issue

  • 4 / 9

Start / End Page

  • 899 - 909

PubMed ID

  • 22700084

Pubmed Central ID

  • PMC3427476

Electronic International Standard Serial Number (EISSN)

  • 1756-591X

International Standard Serial Number (ISSN)

  • 1756-5901

Digital Object Identifier (DOI)

  • 10.1039/c2mt20069d


  • eng