Synthesis and antitumor properties of some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

Keywords: organic synthesis, 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole, antitumor activity


One of the promising methods of creating antitumor drugs is the screening of potential antitumor agents among synthesized compounds. Nitrogen-based heterocycle analogues are an extremely important class of organic substances that are widely used in medical chemistry. [1,2,4]Triazolo[3,4-b][1,3,4] thiadiazoles are among the little-studied and hard-to-reach members of this class of compounds.

The aim of our work was to synthesize some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, as well as the study of their antitumor activity.

The objects of study were 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The composition and structure of the synthesized compounds were confirmed by the data of elemental analysis and 1H NMR spectroscopy. The antitumor activity of the synthesized compounds was studied in the framework of the international scientific program of the National Cancer Institute (Bethesda, Maryland, USA) DTP NCI (Developmental Therapeutic Program).

The synthesis of 11 derivatives of 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was carried out. These substances are obtained by the interaction of 5-arylfuran-2-carboxylic acids with 5-substituted 4-amino-4H-1,2,4-triazolo-3-thiols. Primary screening revealed individual 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, which showed pronounced selective antitumor activity. The most active among the tested compounds were 3 d, 3 e and 3 j, which were further investigated during secondary screening. The results of these studies confirm the high antitumor activity of these compounds.

The proposed approaches and the developed synthesis protocols made it possible to obtain a series of new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The results of studies of the antitumor activity of the synthesized compounds made it possible to single out 3 highly active compounds with high antitumor activity, which gives reason to consider this condensed system as a promising molecular framework for the design of potential antitumor agents.


Sung H., Ferlay J., Siegel R. et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries // CA: A Cancer J. Clin. – 2021. – V. 71, N 3 – P. 209–249.

Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review) // Inter. J. Oncol. – 2019. – V. 54, N 2 – P. 407–419.

Kerru N., Gummidi L., Maddila S. et al. A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications // Molecules. – 2020. – V. 25, N 8 – P. 1909–1951.

Leliukh M. I. Biolohichna aktyvnist heterotsyklichnykh system na osnovi funktsionalno zamishchenykh 1,3,4-tia(oksa)diazoliv (ohliad) // Farmats. zhurn. – 2019. – T. 74, № 6. – C. 43–53.

Kumar D., Kumar J. A Comprehensive Review of N-Heterocycles as Cytotoxic Agents // Current Med. Chem. – 2016. – V. 23, N 38. – P. 4338–4394.

Asif M. A Mini Review: Biological Significances of Nitrogen Hetero Atom Containing Heterocyclic Compounds // Inter. J. Bioorg. Chem. – 2017. – V. 2, N 3. – P. 146–152.

Khattab T., Rehan M. A review on synthesis of nitrogen-containing heterocyclic dyes for textile fibers – Part 2: Fused heterocycles // Egyptian J. Chem. – 2018. – V. 61, N 6. – P. 989–1018.

Sonawane R., Mohite S. Heterocyclic Bridgehead Nitrogen Atom System: Review on [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazole and Its Pharmacological Screening // Asian J. Res. Chem. – 2021. – V. 14, N 3. – P. 217–220.

Ibrahim D. Synthesis and biological evaluation of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as a novel class of potential anti-tumor agents // Eur. J. Med. Chem. – 2009. – V. 44, N 7. – P. 2776–2781.

Kamel M., Megally Abdo N. Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents // Eur. J. Med. Chem. – 2014. – V. 86. – P. 75–80.

Rostom S., Badr M., Razik H. et al. Structure-based development of novel triazoles and related thiazolotriazoles as anticancer agents and Cdc25A/B phosphatase inhibitors. Synthesis, in-vitro biological evaluation, molecular docking and in-silico ADME-T studies // Eur. J. Med. Chem. – 2017. – V. 139. – P. 263–279.

Kumar G., Prasad Y., Mallikarjuna B. et al. Synthesis and pharmacological evaluation of clubbed isopropylthiazole derived triazolothiadiazoles, triazolothiadiazines and Mannich bases as potential antimicrobial and antitubercular agents // Eur. J. Med. Chem. – 2010. – V. 45, N 11. – P. 5120–5129.

Cui P., Li X., Zhu M. et al. Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo- thiadiazole as SecA inhibitors // Eur. J. Med. Chem. – 2017. – V. 127. – P. 159–165.

Jubie S., Ramesh P., Dhanabal P. et al. Synthesis, antidepressant and antimicrobial activities of some novel stearic acid analogues // Eur. J. Med. Chem. – 2012. – V. 54. – P. 931–935.

Deng X., Dong Z., Song M. et al. Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives // Archiv der Pharmazie. – 2012. – V. 345, N 7. – P. 565–573.

Bonafoux D., Nanthakumar S., Bandarage U. et al. Fragment-Based Discovery of Dual JC Virus and BK Virus Helicase Inhibitors // J. Med. Chem. – 2016. – V. 59, N 15. – P. 7138–7151.

Khan I., Ibrar A., Zaib S. et al. Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: Synthesis, crystal structure determination, cytotoxicity, cholinesterase inhibitory activity, and binding mode analysis // Bioorg. Med. Chem. – 2014. – V. 22, N 21. – P. 6163–6173.

Ram S., Celik G., Khloya P. et al. Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII // Bioorg. Med. Chem. – 2014. – V. 22, N 6. – P. 1873–1882.

Yuan H., Liu Q., Zhang L. et al. Discovery, optimization and biological evaluation for novel c-Met kinase inhibitors // Eur. J. Med. Chem. – 2018. – V. 143. – P. 491–502.

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How to Cite
MyrkoI. І., HorakY. І., Chaban, T. I., DrapakІ. V., & Matiychuk, V. S. (2021). Synthesis and antitumor properties of some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles . Farmatsevtychnyi Zhurnal, (5), 37-49.
Synthesis and analysis of biologically active compounds