Synthesis and study of the anticancer activity of some new 7H-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazines




organic synthesis, NMR spectroscopy, triazolo[3,4-b][1,3,4]thiadiazines, anticancer activity


The problem of finding effective low-toxic anticancer agents is one of the most important in modern medicine and pharmacy. Despite a large selection of anticancer drugs and a variety of mechanisms of their action, the effectiveness of existing drugs continues to be insufficient. Among the numerous natural and synthetic heterocyclic compounds that exhibit anticancer activity, 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives, which are able to initiate different pathways of tumor cell death. Based on this, the synthesis of new derivatives of this class of compounds and the study of their anticancer properties is relevant.

The aim of the work is to synthesis of new 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and study their anticancer activity.

Materials and methods. It was used methods of organic synthesis, physical and chemical methods of analysis organic compounds (1H NMR spectroscopy, elemental analysis).

Results. In order to obtain new 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, the interaction implemented of 4-amino-4H-[1,2,4]triazole-3-thiols with the corresponding bromoacetophenones. The reaction proceeds by heating the above reagents in alcohol with the closure of the thiadiazine ring and the formation of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine systems. The structure of all synthesized compounds was confirmed by 1H NMR spectroscopy and elemental analysis data.

The study of the anticancer activity of the synthesized compounds was carried out in the framework of the international scientific program DTP (Developmental Therapeutics Program) of the National Cancer Institute (NCI, Bethesda, Maryland, USA). It was found that the synthesized compounds exhibited different levels of anticancer activity. The most active among the tested substances was compound 3j with an average GP value of 28.73. The most sensitive to it were the lines of melanoma MDA-MB-435 and SK-MEL-2, kidney cancer A498 and RXF 393, CNS cancer SNB-75, and non-small cell lung cancer NCI-H522. The secondary stage of studies of this compound confirmed its high anticancer activity against most cancer cell lines.

Conclusions. As a result of the interaction of 4-amino-4H-[1,2,4]triazole-3-thiols with the relevant bromoacetophenones, a series of new triazolo[3,4-b][1,3,4]thiadiazines was not described in the literature was synthesized. Testing the synthesized compounds for the antitumor activity made it possible to isolate 1 highly active compound with a pronounced anticancer effect, which in terms of activity approaches or exceeds the known drugs 5-fluorouracil (5-FU) and cisplatin, as well as an anticancer agent, curcumin.


Author Biographies

I. I. Myrko, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

Assistant of the Department of General, Bioinorganic, Physical and Colloidal Chemistry

T. I. Chaban, Danylo Halytsky Lviv National Medical University, Ukraine

PhD, Associate Professor of the Department of General, Bioinorganic, Physical and Colloidal Chemistry

V. V. Ohurtsov, Danylo Halytsky Lviv National Medical University, Ukraine

PhD, Associate Professor of the General, Bioinorganic, Physical and Colloidal Chemistry

I. V. Drapak, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

DSc, Professor, Head of the Department of General, Bioinorganic, Physical and Colloidal Chemistry

V. S. Matiichuk, Ivan Franko National University of Lviv, Lviv, Ukraine

DSc, Professor of the Department of Organic Chemistry


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How to Cite

Myrko II, Chaban TI, Ohurtsov VV, Drapak IV, Matiichuk VS. Synthesis and study of the anticancer activity of some new 7H-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazines. Current issues in pharmacy and medicine: science and practice [Internet]. 2021Oct.25 [cited 2024Jul.20];14(3):320-7. Available from:



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