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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 effect 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 are potentially useful neuroprotective agents against neurodegenerative diseases.

medchemcomm

Cytoprotective effects of hydrogen sulfide-releasing <i>N</i>-methyl-<scp>d</scp>-aspartate receptor antagonists mediated by intracellular sulfane sulfur

Cytoprotective effects of hydrogen sulfide-releasing N-methyl-d-aspartate receptor antagonists mediated by intracellular sulfane sulfur