Cyclodextrin-derived chalcogenides as glutathione peroxidase mimics and their protection of mitochondria against oxidative damage

  • Aiquan Jiao
  • Na Yang
  • Jinpeng Wang
  • Xueming Xu
  • Zhengyu Jin
Original Article
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Abstract

A series of novel glutathione peroxidase (GPx) mimics based on organochalcogen cyclodextrin (CD) dimer were synthesized. Their GPx-like antioxidant activities were studied using hydrogen peroxide H2O2, tert-butylhydroperoxide (BHP), and cumene hydroperoxide (CHP) as substrates and glutathione as thiol co-substrate. The results showed that 6A,6B-ditelluronic acid-A,6B′-tellurium bridged γ-cyclodextrin (6-diTe-γ-CD) had the highest peroxidase activity, which was ~670-fold higher than ebselen, a well-known GPx mimic. Reduction of lipophilic CHP often proceeded much faster than reduction of the more hydrophilic H2O2 or BHP, which cannot bind into the hydrophobic interior of the CD. The biological activities were also evaluated for their capacity to protect mitochondria against ferrous sulfate/ascorbate-induced oxidative damage. 6-diTe-γ-CD was the best inhibitor which significantly suppressed ferrous sulfate/ascorbate-induced cytotoxicity as determined by swelling of mitochondria, lipid peroxidation and cytochrome c oxidase activity. Our data suggests that 6-diTe-γ-CD has potential pharmaceutical application in the treatment of ROS-mediated diseases.

Keywords

Organochalcogen Gamma-cyclodextrin Glutathione peroxidase Artificial enzyme Mitochondria 
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Notes

Acknowledgments

We are grateful to Dr. Kim for providing language help, Dr. Z.F. Li and C.Y. Ma for their technical assistance, and Miss W.H. Cui and G.Q. Wang for secretarial assistance. This study was supported by National Natural Science Foundation of China (No. 20976070), Project of Education Ministry (No. 109080), Nature Science Foundation of Jiangsu Province (Nos. BK2008003 and BK2009069).

Supplementary material

10847_2012_156_MOESM1_ESM.doc (286 kb)
Supplementary material 1 (DOC 285 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Aiquan Jiao
    • 1
    • 2
  • Na Yang
    • 1
    • 2
  • Jinpeng Wang
    • 1
    • 2
  • Xueming Xu
    • 1
    • 2
  • Zhengyu Jin
    • 1
    • 2
  1. 1.The State Key Laboratory of Food Science and TechnologyJiangnan UniversityWuxiChina
  2. 2.School of Food Science and TechnologyJiangnan UniversityWuxiChina

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