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Antioxidants
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Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and...
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Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and Synthetic Tools for Physiology and Disease

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: 31 May 2026 | Viewed by 3074

Special Issue Editors

Prof. Dr. Giuseppe Caliendo

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Guest Editor
Department of Pharmacy, School of Medicine, University of Naples Federico II, Via D. Montesano 49, 80131 Napoli, Italy
Interests: drug discovery; medicinal chemistry; green chemistry; small molecules; peptides; peptidomimetics; heterocyclic compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Angela Corvino

E-Mail Website
Guest Editor
Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Napoli, Italy
Interests: medicinal chemistry; drug design; synthesis; small-molecules; peptides; peptidomimetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hydrogen sulfide (H2S) is now widely acknowledged as the third endogenous gasotransmitter, joining nitric oxide (NO) and carbon monoxide (CO) as a key regulator of diverse biological processes. It influences numerous physiological systems, including vascular regulation, immune responses, redox balance, and mitochondrial function. Despite its important roles, the full characterization of H2S signaling is limited because of its low endogenous concentrations and rapid reactivity within biological systems. To overcome these challenges and to better define the physio-pathological functions of this gas, natural sources of H2S have been used, and significant efforts have been directed toward the development of synthetic H2S sources. In particular, the design of H2S-donor compounds—capable of releasing the gas in a controlled and physiologically relevant manner—has become an essential strategy for elucidating its functions and therapeutic potential.

We invite you to submit your latest research findings or review articles to this Special Issue, as we aim to gather cutting-edge research focused on the chemistry, biology, and pharmacology of H2S and its donors. This Special Issue offers a multidisciplinary platform for advancing our understanding of sulfur-based signaling in both physiological and pathological contexts, highlighting novel pharmacological tools and mechanistic insights.

We look forward to your valuable contributions.

Prof. Dr. Giuseppe Caliendo
Dr. Angela Corvino
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hydrogen sulfide
  • H2S donors
  • H2S hybrid compounds
  • H2S sources
  • pharmacological tools
  • H2S signaling

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Published Papers (2 papers)

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Research

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16 pages, 2169 KB  
Article
Thiourea-Based H2S-Releasing Pramipexole Hybrids as Neuroprotective Agents
by Angela Corvino, Valentina Citi, Antonia Scognamiglio, Alma Martelli, Vincenzo Calderone, Giulia Neggiani, Carmela Fimognari, Ferdinando Fiorino, Elisa Magli, Rosa Sparaco, Vincenzo Santagada, Giuseppe Caliendo and Beatrice Severino
Antioxidants 2026, 15(5), 628; https://doi.org/10.3390/antiox15050628 - 15 May 2026
Viewed by 184
Abstract
Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson’s disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H2S)-releasing hybrids using, for [...] Read more.
Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson’s disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H2S)-releasing hybrids using, for the first time, a thiourea moiety as an H2S-donating linker to extend the therapeutic profile of pramipexole beyond dopamine receptor agonism. The hybrids were synthesized and characterized, and their H2S-releasing properties were assessed by amperometric and intracellular detection assays. Among the series, compound 2e (PRAM-ADA) showed the most efficient and sustained H2S release, indicating a favorable thiol-dependent release profile. PRAM-ADA was further evaluated for antioxidant and anti-senescent activities in BV2 microglial cells, as well as for chemical and enzymatic stability under simulated physiological conditions. The hybrid significantly reduced LPS-induced reactive oxygen species accumulation and attenuated oxidative stress–induced cellular senescence, demonstrating a superior cytoprotective profile compared with pramipexole. These findings support the concept that combining dopaminergic activity with controlled H2S donation enhances antioxidant and anti-senescent responses, indicating their potential as multitarget agents with neuroprotective properties relevant to neurodegenerative disorders, including PD. Full article
(This article belongs to the Special Issue Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and Synthetic Tools for Physiology and Disease)
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Review

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27 pages, 1252 KB  
Review
Early-Life Hydrogen Sulfide Signaling as a Target for Cardiovascular–Kidney–Metabolic Syndrome Reprogramming
by Chien-Ning Hsu, Ying-Jui Lin, Chih-Yao Hou, Yu-Wei Chen and You-Lin Tain
Antioxidants 2025, 14(9), 1064; https://doi.org/10.3390/antiox14091064 - 29 Aug 2025
Cited by 3 | Viewed by 2253
Abstract
Hydrogen sulfide (H2S), once regarded solely as a toxic gas, is now recognized as a vital endogenous signaling molecule with important roles in both health and disease. Growing evidence supports the developmental origins of health and disease (DOHaD) framework, in which [...] Read more.
Hydrogen sulfide (H2S), once regarded solely as a toxic gas, is now recognized as a vital endogenous signaling molecule with important roles in both health and disease. Growing evidence supports the developmental origins of health and disease (DOHaD) framework, in which early-life disturbances in H2S signaling may drive the later development of cardiovascular–kidney–metabolic (CKM) syndrome—a condition that encompasses chronic kidney disease, obesity, diabetes, and cardiovascular disease. This review highlights the emerging importance of H2S in CKM programming and the potential of H2S-based interventions during gestation and lactation to prevent long-term adverse health outcomes in offspring. Findings from animal studies suggest that maternal supplementation with sulfur-containing amino acids, N-acetylcysteine, H2S donors, and related sulfur-containing biomolecules can attenuate CKM-related risks in progeny. Despite these advances, several critical areas remain underexplored, including the role of gut microbiota-derived H2S, the epigenetic mechanisms influenced by H2S during development, and the clinical translation of preclinical findings. Targeting H2S signaling offers a promising strategy for early-life prevention of CKM syndrome and may also hold broader potential for preventing other DOHaD-related chronic diseases. Full article
(This article belongs to the Special Issue Hydrogen Sulfide, Reactive Sulfur Species, and Donor Compounds: Natural and Synthetic Tools for Physiology and Disease)
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