Biological Effects of Morpholin-4-Ium 4 Methoxyphenyl (Morpholino) Phosphinodithioate and Other Phosphorothioate-Based Hydrogen Sulfide Donors.

Hydrogen sulfide (HS) is regarded as the third gasotransmitter along with nitric oxide and carbon monoxide. Extensive studies have demonstrated a variety of biological roles for HS in neurophysiology, cardiovascular disease, endocrine regulation, and other physiological and pathological processes. Novel HS donors have proved useful in understanding the biological functions of HS, with morpholin-4-ium 4 methoxyphenyl (morpholino) phosphinodithioate (GYY4137) being one of the most common pharmacological tools used. One advantage of GYY4137 over sulfide salts is its ability to release HS in a slow and sustained manner akin to endogenous HS production, rather than the delivery of HS as a single concentrated burst. Here, we summarize recent progress made in the characterization of the biological activities and pharmacological effects of GYY4137 in a range of and systems. Recent developments in the structural modification of GYY4137 to generate new compounds and their biological effects are also discussed. Slow-releasing HS donor, GYY4137, and other phosphorothioate-based HS donors are potent tools to study the biological functions of HS. Despite recent progress, more work needs to be performed on these new compounds to unravel the mechanisms behind HS release and pace of its discharge, as well as to define the effects of by-products of donors after HS liberation. This will not only lead to better in-depth understanding of the biological effects of HS but will also shed light on the future development of a new class of therapeutic agents with potential to treat a wide range of human diseases.