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Review
. 2023 Mar 5;12(3):650.
doi: 10.3390/antiox12030650.

H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity

Qiwei Hu  1 , John C Lukesh 3rd  1
Affiliations
Review

H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity

Qiwei Hu et al. Antioxidants (Basel). .

Abstract

Hydrogen sulfide (H2S) is an endogenous signaling molecule that greatly influences several important (patho)physiological processes related to cardiovascular health and disease, including vasodilation, angiogenesis, inflammation, and cellular redox homeostasis. Consequently, H2S supplementation is an emerging area of interest, especially for the treatment of cardiovascular-related diseases. To fully unlock the medicinal properties of hydrogen sulfide, however, the development and refinement of H2S releasing compounds (or donors) are required to augment its bioavailability and to better mimic its natural enzymatic production. Categorizing donors by the biological stimulus that triggers their H2S release, this review highlights the fundamental chemistry and releasing mechanisms of a range of H2S donors that have exhibited promising protective effects in models of myocardial ischemia-reperfusion (MI/R) injury and cancer chemotherapy-induced cardiotoxicity, specifically. Thus, in addition to serving as important investigative tools that further advance our knowledge and understanding of H2S chemical biology, the compounds highlighted in this review have the potential to serve as vital therapeutic agents for the treatment (or prevention) of various cardiomyopathies.

Keywords: H2S codrugs; H2S donors; MI/R injury; cardioprotection; chemotherapy-induced cardiotoxicity; hydrogen sulfide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Enzymatic and nonenzymatic production of H2S in mammalian systems. PLP: pyridoxal 5′-phosphate; CBS: cystathionine β-synthase; CSE: cystathionine γ-lyase; CAT: cysteine aminotransferase; 3-MST: 3-mercaptopyruvate sulfurtransferase; NADPH: nicotinamide adenine dinucleotide phosphate.
Figure 2
Figure 2
Molecular mechanisms that underscore the cardioprotective effects of H2S, including its ability to combat MI/R injury.
Figure 3
Figure 3
Hydrolysis-triggered H2S release from GYY4137.
Figure 4
Figure 4
Hydrolysis-triggered H2S release from DTTs.
Figure 5
Figure 5
Chemical structures of DTTs and donor hybrids with protective effects against MI/R injury.
Figure 6
Figure 6
pH-triggered H2S release from JK donors.
Figure 7
Figure 7
JK donors with established cardioprotective effects in MI/R injury models.
Figure 8
Figure 8
Thiol-triggered donors with established cardioprotective effects in H/R and MI/R injury models.
Figure 9
Figure 9
Thiol-triggered H2S release from NSHDs.
Figure 10
Figure 10
Thiol-triggered H2S release from acyl perthiols.
Figure 11
Figure 11
Thiol-triggered H2S release from allyl thioesters.
Figure 12
Figure 12
Thiol-triggered H2S release from perthiocarbamates.
Figure 13
Figure 13
Thiol-triggered H2S release from isothiocyanates.
Figure 14
Figure 14
Esterase-triggered H2S release from P2, a donor with cardioprotective effects in MI/R injury models.
Figure 15
Figure 15
β-galactosidase-triggered H2S release from an NO-H2S donor hybrid, a compound with cardioprotective effects in MI/R injury models.
Figure 16
Figure 16
General mechanism for H2S release from ROS-triggered, O-alkyl thiocarbamate-based donors.
Figure 17
Figure 17
ROS-triggered donors with cardioprotective effects in H/R and MI/R injury models.
Figure 18
Figure 18
Protective mechanisms of H2S against chemotherapy-induced cardiotoxicity.
Figure 19
Figure 19
H2S-donating, doxorubicin hybrid codrugs with protective effects against anthracycline-induced cardiotoxicity.
Figure 20
Figure 20
ROS-triggered H2S release from c1, an ROS-responsive DOX hybrid prodrug with reduced cardiotoxicity in rat cardiomyocytes in culture.
See this image and copyright information in PMC

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