New effective compounds, fragments of which can be endogenous donors of an important signaling molecule – hydrogen sulfide in the body, were synthesized by SUSU scientists . Due to this property, the obtained compounds can be used as potential drugs with a cancer-preventing effect. The results of the work, which also reflected a new strategy for the introduction of endogenous donors of hydrogen sulfide, were published in the Russian Chemical Bulletin (Q3).
Organosulfur compounds with anticancer, antibacterial and antirheumatic properties have been studied for a number of years by scientists from South Ural State University together with colleagues from the Institute of Organic Chemistry. N. D. Zelinsky of the Russian Academy of Sciences (IOC RAS). In the latest study, they turned to the search for new derivatives of the class of 1,2-dithiol-3-thiones – compounds with diverse biological activity.
Several years ago, scientists showed that the 1,2-dithiol-3-thione fragment is an effective endogenous donor of hydrogen sulfide in the body. This means that it can increase the gas content in human blood and tissues. One of the most studied hydrogen sulfide donors in the world is 5- (4-hydroxyphenyl) -3H-1,2-dithiol-3-thione (ADT-OH). Scientists have previously developed an efficient method for producing the compound. In the last work, the researchers reflected the strategy of a fundamentally new method of introducing a dithiolthione fragment based on the previously synthesized 4,5-dichloro-1,2-dithiol-3-thione into hybrid molecules.
“ Cellular hydrogen sulfide regulates important functions of the cardiovascular, immune, nervous, respiratory and gastrointestinal systems. A fundamentally new achievement was the introduction of a new heterocyclic fragment containing a dithiolothionic cycle to obtain an endogenous hydrogen sulfide donor containing a natural non-toxic molecule of thioglycoside , ”said Doctor of Chemistry, Professor Oleg Rakitin .
In the joint laboratory of SUSU and the Institute of Organic Chemistry of the Russian Academy of Sciences, together with colleagues from the Pacific Institute of Bioorganic Chemistry. G.B. Elyakov of the Far Eastern Branch of the Russian Academy of Sciences carried out the synthesis and proof of the structure of new compounds. The efficacy was tested in mouse epidermal cell models (JB6 Cl41 P +) and in soft agar human leukemia cell models. The study of cancer preventive (anticancer) activity was carried out at the Pacific Institute of Bioorganic Chemistry. The cooperation of groups working in various fields of science has become a distinctive feature of research.
As a result, the scientists synthesized six new acetylthioglycoside derivatives of 4-chloro-1,2-dithiol-3-thione. It has been established that all of them can be used as potential drugs with anticancer effects.
The research is fundamental. In the future, scientists intend to obtain other compounds, fragments of which can release two or even three endogenously produced signaling molecules of hydrogen sulfide, carbon monoxide and nitric oxide. The results of the study can create a breakthrough in the field of obtaining multipurpose drugs and arouse the interest of organizations specializing in the field of cancer preventive activity.
South Ural State University (SUSU) is a university of digital transformations, where innovative research is carried out in most of the priority areas of development of science and technology. In accordance with the strategy of scientific and technological development of the Russian Federation, the university is focused on the development of large scientific interdisciplinary projects in the field of digital industry, materials science and ecology. In the Year of Science and Technology, SUSU will take part in the competition under the Priority-2030 program. The university performs the functions of a regional project office of the Ural interregional world-class scientific and educational center (UMNOTs).
Reference: Fedorov, S.N., Kuzmich, A.S., Sabutskii, Y.E. et al. Synthesis and studies of acetylthioglycoside conjugates of 4-chloro-1,2-dithiole-3-thione as potential antitumor agents. Russ Chem Bull 70, 573–579 (2021). https://doi.org/10.1007/s11172-021-3127-1
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