Experts Identified the Most Promising Substances for Cancer Treatment
Working together with their colleagues, scientists of Immanuel Kant Baltic Federal University estimated the prospects of new chemical compounds in cancer treatment. These substances can suppress the work of thioredoxin reductase, a multifunctional enzyme that provides several vital cell processes and is extremely active in tumors. The authors not only named the most potentially effective compounds but also suggested their concept of an "ideal" drug. The review was published in the Expert Opinion On Therapeutic Patents journal.
The thioredoxin protein (TRX) is a crucial component for the proper functioning of any organism. It neutralizes active oxygen forms and is a part of RNA synthesis. The proper functioning of this protein is regulated by a specific enzyme called thioredoxin reductase (TrxR). It may become a target of future anti-tumor drugs since the cancer-affected cells have an excessively high metabolism and therefore their TRX systems are hyperactive.
During the research, the specialists identified the basic types of substances that can suppress the effects of thioredoxin reductase. These substances are the metal complexes, arsenic and selenium compounds, Michael acceptors (that include the carbonyl group C=O with a double bond), and nitro-aromatic compounds containing the NO2 group. The scientists explained that there were no significant differences between old and new compounds, but the accumulation of knowledge in this area could help advance practical research. Most of them follow the same pattern: inhibitors (suppressants) bind to active site of the enzyme permanently disabling their function. In therapeutic practice, anti-cancer drugs based on these substances are not being used yet, since they have not been sufficiently investigated.
"In some cases, the anti-tumor action was discovered accidentally when a drug had already been developed and registered for the treatment of other diseases. For example, this is the case with Auranofin—an antirheumatic drug based on a complex of gold. At first, it was not clear how exactly it worked, but in the course of the research it demonstrated its ability to inhibit thioredoxin reductase", - says Mikhail Krasavin, Professor of Medicinal Chemistry and the Head of the Department of Natural Products Chemistry, Institute of Chemistry of Saint Petersburg State University.
Since 2017, many TrxR inhibitors, including some of the new types, have been patented. After analyzing more than forty articles, the researchers from I. Kant BFU concluded that hybrid and dual drugs had the greatest potential. In their structure, the TrxR inhibitory motifs are linked to fragments capable of inhibiting other enzymes that are involved in the emergence and growth of tumors. One example of such a hybrid is a chemical compound studied by a team of Chinese scientists. One active part of the molecule is a fragment of piperlongumine that inhibits TrxR. The other is a fragment of 4-phenymidazole which stimulates the immune system for natural cancer control. As a result, the hybrid has a complex effect reducing tumor growth. In the past 4 years, several substances of this kind were discovered but none of them has yet been used in practice. However, local experts think that these substances can become a basis for full-fledged medicines in the future.
The authors of the article also provided their research. Their substance works on almost the same principle as the others. However, the uniqueness of their development lies in the fact that the chemical substance replicates the structure of thioredoxin, making it faster and more effective to react. According to experiments, this substance is also efficient in "turning off" the TRX system.
Currently, only an ethaneselene-based drug is in an active testing phase. Its properties of suppressing TrxR activity were discovered much earlier. Most of the created inhibitors are potentially toxic to the human body which prevents their usage in therapy. Today it is important to monitor researching trends to find a solution to this problem in the future. This is why the scientists emphasize the importance of their patent analysis.
More information:
www.tandfonline.com/doi/abs/10 … 0?journalCode=ietp20
Provided by Immanuel Kant Baltic Federal University
