Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 22:16:1599816.
doi: 10.3389/fphar.2025.1599816. eCollection 2025.

Synthetic and semi-synthetic antioxidants in medicine and food industry: a review

Jan Tauchen  1 , Lukáš Huml  2 , Michal Jurášek  2 , Joe M Regenstein  3 , Fatih Ozogul  4   5
Affiliations
Review

Synthetic and semi-synthetic antioxidants in medicine and food industry: a review

Jan Tauchen et al. Front Pharmacol. .

Abstract

Oxidative stress is recognized as both a causative and contributing factor in many human diseases. As a result, significant research has been devoted to the development of synthetic and semi-synthetic antioxidants (ATs). This review summarizes the therapeutic potential of synthetic ATs, explores their possible clinical applications, and highlights novel structural modifications aimed at improving their pharmacological properties. Additionally, it presents ideas for refining current antioxidant testing methodologies. Despite the ongoing research, the therapeutic efficacy of synthetic ATs remains ambiguous for several reasons. These include the following: therapeutic benefits resulting from non-antioxidant mechanisms, insufficient dosage to elicit an antioxidant effect, poor oral bioavailability, a narrow therapeutic index, or toxicity that precludes clinical use. Nevertheless, some compounds, such as ebselen, edaravone, MitoQ10, and potentially N-acetylcysteine, have shown promising results. However, further studies are needed to confirm their efficacy and clarify whether their therapeutic effects are truly mediated through antioxidant mechanisms. Dietary antioxidants have achieved relatively higher clinical success, although their toxicity has also led to the withdrawal of some agents. One emerging therapeutic strategy involves inhibition of NADPH oxidase (NOX) enzymatic activity, with compounds such as ebselen, S17834, and GKT137831 showing potential across various disease models. Efforts to enhance antioxidant properties through molecular modifications, using advanced technologies such as prodrug strategies, nanotechnology, polymer complexation, targeted delivery systems, or conversion into inhalable formulations, have yielded variable success. Still, confirming the clinical relevance of newly developed antioxidants will require a paradigm shift in the testing approaches. Future studies must better define the molecular context of antioxidant action, including the following: which biomolecules are being protected, the specific radical species targeted, the tissue and subcellular distribution of the antioxidant, and how levels of endogenous antioxidants and reactive oxygen species (ROS) change post-administration (e.g., within the mitochondria). Despite extensive research, only a few synthetic antioxidants, such as edaravone, are currently used in clinical practice. Currently, no new antioxidant drugs are expected to receive regulatory approval in the near future.

Keywords: chelation therapy; free radical scavenging; oxidative stress; semi-synthetic antioxidants; synthetic antioxidants.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Image depicting sources of ROS/RNS (reactive nitrogen species), their formula, and their impact on human pathology. Note that ROS/RNS not only have deleterious effects, but they also have important physiological roles, including an immune response to bacteria and cancer cells and molecular signaling (Halliwell, 2024). Created with Biorender.com.
FIGURE 2
FIGURE 2
Number of articles containing the search keywords (compound names) in the title/abstract from 1960 to 2024 and merged into the corresponding categories. Data retrieved from PubMed on 3 December 2024. Note: the figure suggests that thiols (especially N-acetylcysteine, since it accounts for more than 50% of total number of citations on thiol), vitamin E/C derivatives, and related chain-breaking ATs are the most researched synthetic ATs. Mitochondria-targeted ATs are also attracting considerable research attention over the last decade.
FIGURE 3
FIGURE 3
(A) Mechanism of superoxide dismutase and catalase. (B) One-electron-transferring manganese-containing SOD mimetics. (C) SOD/catalase mimetics of the EUK series. (D) Porphyrin-based SOD/catalase mimetics. Created with Biorender.com.
FIGURE 4
FIGURE 4
Chemical structures of spin traps/nitroxides.
FIGURE 5
FIGURE 5
AT cycle of GPx and glutathione peroxidase mimetics. Created with Biorender.com.
FIGURE 6
FIGURE 6
(A) The AT network of vitamins E and C and thiols. (B) Synthetic vitamin E analogs. (C) Synthetic vitamin C analogs.
FIGURE 7
FIGURE 7
Chain breaking AT. (*BHA consists of a mixture of two isomers.). (A,B) ATs tested in a medicinal context. (C) ATs of value in the food industry.
FIGURE 8
FIGURE 8
Chemical structures of lazaroids.
FIGURE 9
FIGURE 9
Molecular structure of thiol-based AT. (A) Most frequently studied thiols. (B) Other thiols.
FIGURE 10
FIGURE 10
Structure of mitoquinol (MitoQ10; mitochondria-targeted AT).
FIGURE 11
FIGURE 11
(A) Metal chelators and mechanism of action of DFO. DFO reduces free radical formation, diminishes apoptosis and induces hypoxia inducible factor (HIF) pathway and thus activates angiogenic pathways. (B) Other metal-chelating agents. Created with Biorender.com.
FIGURE 12
FIGURE 12
XO inhibitors based on a purine skeleton.
FIGURE 13
FIGURE 13
Suggested inhibitors of phagocyte-derived RS production and the important mechanism of respiratory burst for killing pathogens in phagocytes. Created with Biorender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Abe K., Morita S., Kikuchi T., Itoyama Y. (1997). Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease. J. Neurosci. Res. 48, 63–70. 10.1002/(sici)1097-4547(19970401)48:1<63::aid-jnr6>3.3.co;2-5 - DOI - PubMed
    1. Adlam V. J., Harrison J. C., Porteous C. M., James A. M., Smith R. A. J., Murphy M. P., et al. (2005). Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J. 19, 1088–1095. 10.1096/fj.05-3718com - DOI - PubMed
    1. Agus D. B., Gambhir S. S., Pardridge W. M., Spielholz C., Baselga J., Vera J. C., et al. (1997). Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters. J. Clin. Invest. 100, 2842–2848. 10.1172/JCI119832 - DOI - PMC - PubMed
    1. Ahola T., Lapatto R., Raivio K. O., Selander B., Stigson L., Jonsson B., et al. (2003). N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial. J. Pediatr. 143, 713–719. 10.1067/S0022-3476(03)00419-0 - DOI - PubMed
    1. Aliev G., Obrenovich M. E., Reddy V. P., Shenk J. C., Moreira P. I., Nunomura A., et al. (2008). Antioxidant therapy in Alzheimer’s disease: theory and practice. Mini Rev. Med. Chem. 8, 1395–1406. 10.2174/138955708786369582 - DOI - PMC - PubMed

LinkOut - more resources