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Review
. 2024 Jun 27;25(13):7014.
doi: 10.3390/ijms25137014.

Pills of Multi-Target H2S Donating Molecules for Complex Diseases

Angela Corvino  1 , Antonia Scognamiglio  1 , Ferdinando Fiorino  1 , Elisa Perissutti  1 , Vincenzo Santagada  1 , Giuseppe Caliendo  1 , Beatrice Severino  1
Affiliations
Review

Pills of Multi-Target H2S Donating Molecules for Complex Diseases

Angela Corvino et al. Int J Mol Sci. .

Abstract

Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs) able to modulate multiple targets of interest, including the pathways where hydrogen sulfide (H2S) is involved. By incorporating an H2S donor moiety into a native drug, researchers have been able to simultaneously target multiple therapeutic pathways, resulting in improved treatment outcomes. This review gives the reader some pills of successful multi-target H2S-donating molecules as worthwhile tools to combat the multifactorial nature of complex disorders, such as inflammatory-based diseases and cancer, as well as cardiovascular, metabolic, and neurodegenerative disorders.

Keywords: H2S donors; hydrogen sulfide; molecular hybridization; multi-target compounds; multi-target directed ligand.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Multi-target drug design strategy of H2S donating molecules based on framework combination. The two moieties, native drug (in blue) and H2S donor (in yellow), can be connected via metabolically stable or cleavable linkers, attached directly (fused) or merged.
Figure 2
Figure 2
Chemical structures of natural H2S donating compounds: garlic-derived organosulfur compounds (yellow box) and natural isothiocyanates from Brassicaceae family (green box).
Figure 3
Figure 3
Chemical structures of most representative H2S donors.
Figure 4
Figure 4
Biological effects and pathophysiological mechanisms of H2S donors.
Figure 5
Figure 5
Chemical structures of representative H2S-NSAIDs.
Figure 6
Figure 6
Chemical structures of representative NOSH-NSAIDs.
Figure 7
Figure 7
Structures of H2S-donating prednisone, dexamethasone, betamethasone and triamcinolone derivatives.
Figure 8
Figure 8
Structures of H2S-donating DOXOs.
Figure 9
Figure 9
Chemical structures of H2S-donating capsaicin derivatives (B1-B14) and of the most interesting of the series (B9).
Figure 10
Figure 10
Chemical structure of H2S-donating metformin.
Figure 11
Figure 11
Chemical structure of H2S-donating AP-39.
Figure 12
Figure 12
Chemical structures of H2S-donating adenosine derivatives.
Figure 13
Figure 13
Chemical structure of H2S-donating sildenafil, ACS6.
Figure 14
Figure 14
Chemical structure of H2S-donating Latanoprost.
Figure 15
Figure 15
Chemical structures of H2S brinzolamide derivatives.
Figure 16
Figure 16
Chemical structures of H2S betaxolol derivatives.
Figure 17
Figure 17
Chemical structures of H2S brimonidine derivatives.
Figure 18
Figure 18
Chemical structures of H2S-donating DOPAs.
Figure 19
Figure 19
Chemical structures of H2S memantine derivatives.
Figure 20
Figure 20
Chemical structure of H2S-donating tacrine.
Figure 21
Figure 21
Chemical structures of H2S-donating rivastigmine derivatives.
Figure 22
Figure 22
Chemical structure of H2S-donating melatonin.
Figure 23
Figure 23
Chemical structure of H2S-donating alendronate.
Figure 24
Figure 24
Chemical structures of H2S-donating molecules in clinical trials.
See this image and copyright information in PMC

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