Heterocycles against AIDS
Russian scientists create new drugs for the treatment of AIDS
Olga Romanovskaya, YURSU
Scientists of the South Ural State University and the N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences (IOH RAS) are investigating polyseraazyrogenous heterocycles - organic compounds that have antiviral effects and can be used to treat AIDS. The collaboration also includes colleagues from the University of Zurich (Switzerland), University College London (UK), the University of North Carolina (USA) and the University of Eastern Finland (Finland). One of the latest scientific articles devoted to the study was published in the journal Bioorganic & Medicinal Chemistry Letters (Q1).
Original heterocycles deactivate viruses
Acquired immunodeficiency syndrome (AIDS) is a severe disease caused by the human immunodeficiency virus (HIV). AIDS is an incurable disease so far, it is impossible to completely destroy the virus with the help of currently known methods, but scientists around the world are working to create drugs that will help cope with this disease.
In 2015, a laboratory for the synthesis of original polyseraazrogenous heterocycles and the search for new compounds with high and diverse biological activity was established at South Ural State University together with the N.D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences.
"From the very beginning, the most promising direction of research seemed to us to study the anticancer activity of this class of compounds, but it suddenly turned out that such compounds can also have high and selective activity against the feline immunodeficiency virus, which is the closest analogue of the human immunodeficiency virus," says Oleg Rakitin, Doctor of Chemical Sciences, Professor.
Scientists have found that compounds of different heterocyclic structures are promising compounds for the fight against AIDS, which is of considerable value for the development of not only chemical, but also biological sciences.
"The main scientific result of our research was the discovery of the general mechanism of action of the polyseraazrogenous heterocycles synthesized by us. It lies in the fact that polyseraazrogenous heterocycles with a highly reactive sulfur-sulfur (or sulfur-selenium) bond can open up in the body with the formation of dithiols that interact with the zinc atom, as if removing it from the virus molecule in the form of protein-zinc-thiol complexes and thereby deactivating it," explains Oleg Rakitin.
It should be noted that previously this kind of action of antiviral drugs was not noted. In the course of the work, among the studied compounds, drugs were found that, together with high antiviral activity, have low toxicity to ordinary cells. The discovery of this mechanism made it possible to discover new classes of heterocyclic polyseraazrogenous compounds as antiviral drugs, as well as the possibility of using these drugs for various viral diseases with a similar type of action.
With structures of synthesized heterocyclic structures with high activity against AIDS
International cooperation to achieve maximum results
A distinctive feature of this study is the high degree of collaboration, in which it was possible to bring together some of the best groups in the world working in various fields of science. Thus, the synthesis and proof of the structure of new compounds took place in the joint laboratory of the IOH RAS and SUSU, studies of activity against the feline immunodeficiency virus at the University of Zurich (Switzerland), studies of the mechanism of action of heterocyclic structures at University College London (UK) and the University of North Carolina (USA), computer modeling of the biological action of our compounds at the University of Eastern Finland (Finland).
"Recently, a group of researchers from the National Institute of Infectious Diseases (Rio de Janeiro, Brazil) joined our consortium, which is researching drugs against Sporotrichosis infection, which is especially common in Brazil. It should be noted that each group uses the most modern methods in its research, which allows achieving high results, which are expressed in numerous publications in prestigious journals," Oleg Alekseevich emphasizes.
The research results are presented to the academic community at a number of prestigious conferences, including the American Chemical Society.
Currently, research is at the stage of searching for optimal structures (with the maximum value of the therapeutic index) for each type of disease. The importance of the results obtained is that the same drugs can be used for different types of diseases (cancer, HIV, etc.), which makes their development interesting in practical terms. The study of the action of previously synthesized compounds will be continued for the treatment of other diseases with a similar mechanism of action.
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