- Cyclic Sulfenyl Thiocarbamates Release Carbonyl Sulfide and Hydrogen Sulfide Independently in Thiol-Promoted Pathways
-
Hydrogen sulfide (H2S) is an important signaling molecule that provides protective activities in a variety of physiological and pathological processes. Among the different types of H2S donor compounds, thioamides have attracted attention due to prior conjugation to nonsteroidal anti-inflammatory drugs (NSAIDs) to access H2S-NSAID hybrids with significantly reduced toxicity, but the mechanism of H2S release from thioamides remains unclear. Herein, we reported the synthesis and evaluation of a class of thioamide-derived sulfenyl thiocarbamates (SulfenylTCMs) that function as a new class of H2S donors. These compounds are efficiently activated by cellular thiols to release carbonyl sulfide (COS), which is quickly converted to H2S by carbonic anhydrase (CA). In addition, through mechanistic investigations, we establish that COS-independent H2S release pathways are also operative. In contrast to the parent thioamide-based donors, the SulfenylTCMs exhibit excellent H2S releasing efficiencies of up to 90percent and operate through mechanistically well-defined pathways. In addition, we demonstrate that the sulfenyl thiocarbamate group is readily attached to common NSAIDs, such as naproxen, to generate YZ-597 as an efficient H2S-NSAID hybrid, which we demonstrate releases H2S in cellular environments. Taken together, this new class of H2S donor motifs provides an important platform for new donor development.
- Pluth, Michael D.,Steiger, Andrea K.,Zhao, Yu
-
-
- COMPOUNDS FOR THIOL-TRIGGERED COS AND/OR H2S RELEASE AND METHODS OF MAKING AND USING THE SAME
-
Disclosed herein are embodiments of a compound that is capable of releasing COS and/or H2S upon reaction with a thiol-containing compound. The compound embodiments also can produce a detectable signal (e.g., a fluorescent signal) substantially concomitantly with COS and/or H2S release and/or can release an active agent, such as a therapeutic agent. Methods of making and using the compound embodiments also are disclosed.
- -
-
Page/Page column 34
(2019/12/25)
-
- NOVEL SULFURIZING REAGENT 3-PHENYL-1,2,4-DITHIAZOLINE-5-ONE
-
In our research, 3-phenyl-1,2,4-dithiazoline-5-one is found to be a potential sulfur-transfer reagent. The efficiency and optimization of this new sulfur-transfer reagent was investigated by solid-phase syntheses of dinucleotide phosphorothioate and 25 me
- -
-
-
- Thioacyl Isocyanates, XII. Preparation and Comparison of Aliphatic, Aromatic, and Heteroaromatic Compounds
-
Many 1,2,4-dithiazol-3-ones (2), especially with aliphatic and heterocyclic substituents, and some thiazoline-4,5-diones (3) were synthesized from thioamides (1).Extrusion of sulfur or carbon monoxide, respectively, afforded the thioacyl isocyanates 5.Rea
- Goerdeler, Joachim,Nandi, Kumaresh
-
p. 549 - 563
(2007/10/02)
-