Cytoprotective effects of hydrogen sulfide-releasing N-methyl-d-aspartate receptor antagonists mediated by intracellular sulfane sulfurElectronic supplementary information (ESI) available. See DOI: 10.1039/c4md00180j

Hydrogen sulfide (H 2 S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H 2 S in neurodegenerative diseases may be mediated by N -methyl- d -aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H 2 S while minimizing its toxicity, we synthesized a series of H 2 S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP + )-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effects of H 2 S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H 2 S, levels. These studies suggest that H 2 S-donor compounds that increase intracellular sulfane sulfur levels are potentially useful neuroprotective agents against neurodegenerative diseases. Hydrogen sulfide (H 2 S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection.