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Review
. 2017 Jul 10:8:457.
doi: 10.3389/fphar.2017.00457. eCollection 2017.

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

Jianming Kang  1 , Deshka L Neill  1 , Ming Xian  1
Affiliations
Review

Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications

Jianming Kang et al. Front Pharmacol. .

Abstract

Hydrogen sulfide (H2S) is a newly recognized gasotransmitter. Studies have demonstrated that the production of endogenous H2S and the exogenous administration of H2S can regulate many physiological and/or pathological processes. Therefore, H2S releasing agents (also known as H2S donors) are important research tools in advancing our understanding of the biology and clinical potential of H2S. Among currently available donors, GYY4137 is probably the most well-known and has been used in many studies in the past 10 years. Recently, a number of GYY4137 derivatives (e.g., phosphonothioate-based compounds) have been developed as H2S donors. In this review, we summarize the development and application of these donors, which include Lawesson's reagent, substituted phosphorodithioates, cyclic phosphorane analogs, and pH-controlled phosphonamidothioates (JK donors). These donors have advantages such as good water-solubility, slow and controllable H2S release capability, and a variety of reported biological activities. However, it should be noted that the detailed H2S release profiles and byproducts under real biological systems are still unclear for many of these donors. Only after we figure out these unknowns we will see better applications of these donors in H2S research and therapy.

Keywords: H2S; donor; hydrogen sulfide; pH; phosphonothiolate.

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Figures

FIGURE 1
FIGURE 1
Enzymatic production of H2S.
FIGURE 2
FIGURE 2
Lawesson’s reagent.
FIGURE 3
FIGURE 3
The structure of GYY4137 and its control compound.
FIGURE 4
FIGURE 4
O-Substituted phosphorodithioates.
FIGURE 5
FIGURE 5
Structures of representative GYY4137 analogs.
FIGURE 6
FIGURE 6
The structures of selected JK donors and the H2S release mechanism.
See this image and copyright information in PMC

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