RT: Russian scientists develop compounds to fight cancer
Russian scientists have teamed up with their foreign colleagues to synthesise a line of compounds capable of triggering the process of destroying proteins critical for cancer cells. This was reported to RT by the Russian Science Foundation. The authors of the research have developed compounds that are non-toxic to healthy tissues and can inhibit the activity of malignant cells. The researchers do not exclude that the resulting substances can become the basis for anti-cancer drugs.
The scientists from St Petersburg University, Immanuel Kant Baltic Federal University (Kaliningrad), Togliatti State University together with their foreign colleagues have synthesised a number of compounds for the targeted destruction of cancer cells. This was reported to RT by the press service of the Russian Science Foundation.
The molecular method of fighting cancer is considered to be one of the most promising. This method consists of selectively destroying specific proteins that are vital to the functioning of cancer cells.
Scientists use the natural mechanism of intracellular cleaning of damaged proteins. In the normal state, such proteins that can disrupt normal cell function are detected by a special enzyme − ubiquitinase. It attaches another protein, ubiquitin, to the protein chain, which becomes a "black spot" for it. Such a "tagged" protein molecule is quickly destroyed by special cellular organelles − proteasomes.
The idea to use this mechanism to destroy specific proteins in cancer cells arose in the scientific community in the early 2000s. Its essence is to use a mediator molecule to combine the enzyme ubiquitinase with the protein to be destroyed. The resulting structure is referred to by chemists as a chimera molecule. The substance that serves as the ‘coupling’ between the enzyme and the protein is called a "ligand" and the entire technology for targeting proteins is called PROTAC (PROteolysis Targeting Chimeras).
‘These days, billions of dollars are invested in the development of drugs based on chimeric molecules, and almost every major pharmaceutical company wants them in its portfolio. Chimeric constructs of this type are the ideal "killer", as they can be made for almost any desired target protein. At the same time, they work in the cell in extremely low concentrations, which helps avoid side effects,’ Mikhail Krasavin, Principal Investigator, Doctor of Chemistry, Head of the Laboratory of Synthesis of Biologically Active Small Molecules at St Petersburg University, told RT.
To date, research in this area is ongoing in several countries, and some developments are at the stage of clinical trials. Most often, molecules of the already known immunomodulatory drugs, i.e. thalidomide and its close analogues, act as a "bridge" for protein binding. However, the use of these substances by pregnant women has previously been found to cause severe developmental disorders in children. However, the scientists from Russia, together with their foreign colleagues, have found an alternative to the potentially dangerous compounds. The chemists have synthesised 20 different molecules based on glutarimide, an organic nitrogen-containing substance that is non-toxic and readily binds to enzymes and proteins inside the cell. Glutarimide is already used in pharmacology as a component of drugs with sedative and psychostimulant effects.
The authors of the work have tested the obtained molecules in vitro in experiments on live cancer cells. Sulphur-containing compounds performed best: they were twice as effective at binding to the enzyme and target protein as their existing counterparts. The new molecules were able to inhibit the activity of bone marrow cancer cells without causing toxic effects.
‘In future, we will study the anti-tumour effect of our molecules in more detail to find out why the sulphur-containing compounds prove to be the most active,’ said Mikhail Krasavin.
According to the scientists, the resulting compounds could become the basis for a number of anti-cancer drugs in future.