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

Jan Tauchen^1*Lukáš Huml²Michal Jurášek²Joe M Regenstein³Fatih Ozogul⁴

• ¹Czech University of Life Sciences Prague, Prague, Czechia
• ²University of Chemistry and Technology in Prague, Prague, Prague, Czechia
• ³Cornell University, Ithaca, New York, United States
• ⁴Çukurova University, Adana, Adana, Türkiye

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 ongoing research, the therapeutic efficacy of synthetic ATs remains ambiguous for several reasons. These include: 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 greater clinical success, although toxicity has also led to the withdrawal of some agents. One emerging therapeutic strategy involves inhibition of NADPH oxidase (NOX) enzymes, with compounds such as ebselen, S17834, and GKT137831 showing potential across various disease models.Efforts to enhance antioxidant properties through molecular modification, 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 testing approaches. Future studies must better define the molecular context of antioxidant action, including: 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 mitochondria). Despite extensive research, only a few synthetic antioxidants, such as edaravone, are currently used in clinical practice. At present, no new antioxidant drugs are expected to receive regulatory approval in the near future.