The consensus view of the scientific community is that bioactive compounds are non-essential and essential compounds, found in small amounts in nature and specifically in plants and certain foods. They are part of the food chain and their consumption influences human health. There are plenty of bioactive compounds and some of the most known are polysaccharides, lycopene, dithiolethiones and others. (1,2)
What is a Dithiolethione?
Dithiolethiones are a class of effective cancer chemopreventive agents of which the unsubstituted parent compound, 1, 2-dithiole-3-thione, is the most potent. (3)
The first synthesis of a compound of this class appears to have been by the Italian chemist G.A. Barbaglia in 1884. 3H-1,2-dithiole-3-thione (D3T,) was first synthesized in 1948. Very few dithiolethiones achieved commercial success and only two, 5-(4-methoxyphenyl)-3H-1,2-dithiole-3-thione(ADT) and 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (oltipraz), moved on to efficacy trials in humans with regard to therapeutic use. The scientific interest increased after subsequent studies by Bueding and others, showing that oltipraz prevented several carcinogens from causing DNA damage and cancer in animals.
Although no dithiolethione has yet been approved for cancer prevention in humans, the
wealth of knowledge accumulated on these compounds, particularly oltipraz, offers both guidance and lessons for further research and development of this interesting family of compounds for cancer prevention. (4)
Sources of dithiolethiones
Dithiolethiones are found in cruciferous vegetables, which include the following vegetables, among others: Arugula, Bok choy, Broccoli, Brussels sprouts, Cabbage, Cauliflower, Collard greens, Horseradish, Kale, Radishes, Rutabaga, Turnips, Watercress, Wasabi. (5)
Health benefits of Dithiolethiones
Chemoprotection by dithiolethiones
Dithiolethiones have recently attracted the scientific attention as potential cancer chemopreventive agents. Some compounds of this type, 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (oltipraz) have been shown to protect against carcinogenesis at various organ sites in animal models. Oltipraz and 5-(4-methoxyphenyl)-3H-1,2-dithiole-3-thione have also been evaluated in humans, but the available data show moderate chemo-preventive activities. (6)
One of the mechanisms that play a key role for the protection against mutagenesis, carcinogenesis and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes. The other mechanism is related to the enhanced production of nucleophiles for trapping of reactive carcinogen species.
Scientists tried to test the hypothesis that enzyme induction is an effective way for chemoprevention in humans and conducted a trial in Chinese who were exposed to dietary aflatoxins and who were at high risk for the development of liver cancer. It was reported that administration of 500 mg oltipraz once a week, led to a significant reduction in the excretion of the primary oxidative metabolite of aflatoxin B1, highlighting the feasibility of dithiolethioles to induce phase 2 enzymes in humans. (7)
The chemo-preventive efficacy of oltipraz was also demonstrated in a 2004 study. In this study scientists administered oltipraz in mice and concluded that it prevents urinary bladder carcinogenesis by enhancing detoxification of specific carcinogens. (8)
Schistosomiasis and dithiolethiones
In humans, one of the dithiolethiones known for their pharmacological properties other than cancer chemoprevention is oltipraz, which was originally used as an investigational drug for the treatment of schistosomiasis. Single oral doses of oltipraz were very effective, achieving cure rates of >90% in field trials. (9)
Liver ‘s diseases and Dithiolethiones
A 2009 review investigated the relation between dithiolethiones and hepatocyte protection from inflammation, intoxication and disrupted energy metabolism. Researchers concluded that dithiolethiones may be associated with antioxidant and anti-inflammatory effects. They also highlighted the therapeutic potential of dithiolethione compounds that may offer the possibility of better management or treatment for hepatic diseases. (10)
Researchers during an earlier study (2007) investigated the effects of Oltipraz and other synthetic dithiolthiones on hepatic insulin resistance and the molecular basis of action. Oltipraz prevented hepatic insulin resistance in the animal subjects and the synthetic dithiolthiones had a similar effect, inhibiting insulin resistance. (11)
Antimicrobial activity of dithiolethiones
In a recently published paper, scientists tried to evaluate the potential of some dithiolethiones on standard microorganism strains and multidrug resistant bacteria, which were isolated from hospitals. The compounds of the study possessed antibacterial activity against Gram-positive bacteria. According to previous studies two dithiolethiones compounds, particularly (4-phenyl-1,2-dithiole-3-thione), exhibited biological activity against Staphylococcus aureus. (3)
Dithiolethiones as neuroprotective agents
An American scientific group, recently (2016) published a paper about the potential neuroprotective role of dithiolethiones. The neuroprotective properties of dithiolethiones suggest a role as potential anti-parkinsonian agents. The findings of this study demonstrate that dithiolethiones are promising and potential neuroprotective, antiparkinsonian agents. (12)
Dithiolethiones are very promising chemo-protective candidates for use in the targeted prevention or suppression of cancer in high risk populations. Additionally, dithiolethiones can potentially affect many other health conditions. Eating cruciferous vegetables is important to get some dithiolethiones, but the extra supplementation may help you fulfill your body’s dithiolethiones’ requirements.