Abstract
Hydrogen sulfide (H2S) is a signaling molecule which plays regulatory roles in many physiological and/or pathological processes. Therefore, regulation of H2S levels could have great potential therapeutic value. In this work, we report the design, synthesis, and evaluation of a class of N-mercapto (N-SH)-based H2S donors. Thirty-three donors were synthesized and tested. Our results indicated that controllable H2S release from these donors could be achieved upon structural modifications. Selected donors (NSHD-1, NSHD-2, and NSHD-6) were tested in cellular models of oxidative damage and showed significant cytoprotective effects. Moreover, NSHD-1 and NSHD-2 were also found to exhibit potent protective effects in a murine model of myocardial ischemia reperfusion (MI/R) injury.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzamides / chemical synthesis
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Benzamides / chemistry
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Benzamides / pharmacology
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Cardiotonic Agents / chemical synthesis
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Cardiotonic Agents / chemistry*
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Cardiotonic Agents / pharmacology
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Cell Line
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Drug Design
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Heart Ventricles / cytology
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Hydrogen Peroxide / pharmacology
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Hydrogen Sulfide / metabolism*
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L-Lactate Dehydrogenase / metabolism
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Male
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Membrane Potential, Mitochondrial / drug effects
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Mice, Inbred C57BL
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Myoblasts, Cardiac / cytology
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Myoblasts, Cardiac / drug effects
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Myocardial Reperfusion Injury / drug therapy
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Oxidative Stress
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Rats
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Structure-Activity Relationship
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Sulfhydryl Compounds / chemical synthesis
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Sulfhydryl Compounds / chemistry*
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Sulfhydryl Compounds / pharmacology
Substances
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Benzamides
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Cardiotonic Agents
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Sulfhydryl Compounds
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Hydrogen Peroxide
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L-Lactate Dehydrogenase
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Hydrogen Sulfide