title: Hydrogen Sulfide Donors Activated by Reactive Oxygen Species.
abstract: Hydrogen sulfide (H2S) exhibits promising protective effects in many (patho)physiological processes, as evidenced by recent reports using synthetic H2S donors in different biological models. Herein, we report the design and evaluation of compounds denoted PeroxyTCM, which are the first class of reactive oxygen species (ROS)-triggered H2S donors. These donors are engineered to release carbonyl sulfide (COS) upon activation, which is quickly hydrolyzed to H2S by the ubiquitous enzyme carbonic anhydrase (CA). The donors are stable in aqueous solution and do not release H2S until triggered by ROS, such as hydrogen peroxide (H2O2), superoxide (O2-), and peroxynitrite (ONOO-). We demonstrate ROS-triggered H2S donation in live cells and also demonstrate that PeroxyTCM-1 provides protection against H2O2-induced oxidative damage, suggesting potential future applications of PeroxyTCM and similar scaffolds in H2S-related therapies.
authors: Department of Chemistry and Biochemistry, Institute of Molecular Biology, and Materials Science Institute, University of Oregon, Eugene, OR, 97403, USA.
authors: Yu
authors: Y
authors: Zhao
authors: Department of Chemistry and Biochemistry, Institute of Molecular Biology, and Materials Science Institute, University of Oregon, Eugene, OR, 97403, USA.
authors: Michael D
authors: 0000-0003-3604-653X
authors: MD
authors: Pluth
mesh_terms: D000818:Animals; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002256:Carbonic Anhydrases; D006862:Hydrogen Sulfide
keywords: carbonyl sulfide; hydrogen sulfide; oxidative stress; reactive oxygen species; thiocarbamate