Dihydroxyfumaric Acid: A Review of Transformations, New Derivatives, Importance, and Applications

Introduction

The last decades have been characterized by an increased interest in research related to the discovery of disease prevention possibilities, especially related to minimizing the role of free radicals. Studies concerning the biology and medicine of free radicals are expanding rapidly, because these compounds have an important role in human health and, therefore, in the quality of life (Martemucci et al., 2022).

Recent studies have demonstrated that free radicals perform multiple important biological functions, for example, reactive oxygen species (ROS) and reactive nitrogen species (RNS) operate together with reactive halogen species (RHS) as part of the cellular immune response to infection with microorganisms (Ferrari et al., 2011; Shields et al., 2021), and even exhibit signaling functions, activating specific biochemical pathways inside the cell (Shields et al., 2021; Stone & Yang, 2006). For good physiological functioning, a balance between free radicals and their deactivation systems is necessary. If free radicals overwhelm the body's ability to regulate them, a condition known as oxidative stress occurs (Shields et al., 2021; Lobo et al., 2010), correlated with an increased incidence of degenerative diseases such as cancer, cardiovascular disease, cataracts, liver disease, inflammation, renal insufficiency etc. (Bhuiyan et al., 2009; Duca & Sychev, 2002). Thus, at high concentrations, the interaction of these species with lipid membranes, nucleic acids, proteins, enzymes, or other small molecules, inevitably leads to cell damage. A proven way to counteract the action of excessive free radical formation is the use of antioxidants and free radical scavengers of natural and synthetic origin, which destroy the damaging species and preserve the cells’ healthy condition.

Another direction significantly influenced by the formation of free radicals, equally important and closely related to human health, is the food industry. Food products containing fats and oils, such as meat, cold cuts, vegetable oils, dairy products and bakery products, are susceptible to oxidation due to their chemical composition (Garg et al., 2022). The organoleptic changes occur during long-term storage of food products, especially due to the auto-oxidation process of unsaturated fatty acids, which are more vulnerable to rancidity due to their lower stability compared to saturated fatty acids.

A widely used method to prevent oxidation is to enrich foods with antioxidants during processing and preservation. The mechanisms of action of antioxidants are different, including control of pro-oxidants, inactivation of free radicals and control of oxidation-prone substrates (unsaturated fatty acids and oxygen). However, the industry mostly uses synthetic additives, which are viewed with caution or even negatively by modern consumers, who prefer natural antioxidants and foods without synthetic additives (Poljsak et al., 2021; Pokorny & Smidt, 2001; Bensid et al., 2020).

A large number of organic acids and their salts are already approved for use in the food industry, for example malic (E296), tartaric (E334), ascorbic (E300), lactic (270), succinic (E363) acids (Ben Braiek & Smaoui, 2021). Lactic, citric, and tartaric acids are also widely used in the pharmaceutical and cosmetic industry (Goyal & Jerold, 2021).

Continuous efforts are being made persistently to find new potential compounds with potential antioxidant/antiradical properties with the ultimate goal of enhancing the quality of human life. In this context, the research related to dihydroxyfumaric acid (DHF) and obtaining new derivatives from it, is a promising direction with wide applicability.