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A new tetrazole-containing 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine derivative: synthesis, interaction with DNA, and antitumor activity

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Abstract

({5-[4,6-Di(aziridin-1-yl)-1,3,5-triazin-2-yl]amino}-2,2-dimethyl-1,3-dioxan-5-yl)-methyl 2-(5-phenyl-2H-tetrazol-2-yl)acetate was synthesized and characterized. The interaction of the obtained tetrazole-containing 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine derivative with DNA was studied by UV spectrophotometry, circular dichroism spectroscopy, and isothermal calorimetry. The values of binding constants (9.65·108 L mol−1, UV spectrophotometry; 4.08·108 L mol−1, isothermal calorimetry) of the 1,3,5-triazine derivative to DNA attests to efficient binding and formation of stable associates with the biopolymer. The addition of the tetrazole-containing 1,3,5-triazine derivative to a DNA solution has virtually no effect on the DNA melting point. The tetrazole-containing 1,3,5-triazine derivative exhibits a cytostatic effect on SK-HEP-1 human hepatic adenocarcinoma cells (half-maximal inhibitory concentration IC50 22.2 mmol L−1) and T98G human glioblastoma cells (IC50 44.9 mmol L−1).

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Authors and Affiliations

  1. Akad. I. P. Pavlov First State Medical University of Saint Petersburg, 6-8 ul. L’va Tolstogo, 197022, St. Petersburg, Russian Federation

    O. V. Mikolaichuk, V. V. Sharoyko, E. A. Popova, A. V. Protas, Yu. A. Anufrikov, A. M. Malkova & K. N. Semenov

  2. Saint Petersburg State University, 7/9 Universitetskaya nab., 199034, St. Petersburg, Russian Federation

    O. V. Mikolaichuk, V. V. Sharoyko, A. M. Malkova & K. N. Semenov

  3. Akad. A. M. Granov Research Center for Radiology and Surgical Technologies, Ministry of Health of the Russian Federation, 70 ul. Leningradskaya, pos. Pesochnyi, 197758, St. Petersburg, Russian Federation

    O. V. Mikolaichuk, E. A. Popova, A. V. Protas, O. E. Molchanov & D. N. Maistrenko

  4. Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky prosp., 194064, St. Petersburg, Russian Federation

    A. V. Fonin

  5. Saint Petersburg State Institute of Technology (Technical University), 26 Moskovsky prosp., 190013, St. Petersburg, Russian Federation

    N. T. Shmaneva & V. A. Ostrovskii

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  1. O. V. Mikolaichuk
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  2. V. V. Sharoyko
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  9. V. A. Ostrovskii
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  10. O. E. Molchanov
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  11. D. N. Maistrenko
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Corresponding author

Correspondence to V. V. Sharoyko.

Additional information

Based on materials of the All-Russian Congress on the Chemistry of Heterocyclic Compounds KOST-2021 (October 12–16, 2021, Sochi, Russia).

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1050–1056, May, 2022.

The authors are grateful to resource centers (RC) of the Saint Petersburg State University: RC “Thermogravimetric and Calorimetric Investigation Methods”; RC “Methods for Analysis of Compositions of Compounds”, and RC “Magnetic Resonance Investigation Methods”.

This study was financially supported by the Ministry of Health of the Russian Federation (State Assignment on the Subject “Development and Antitumor Activity Assays of Conjugates of Non-annulated 1,3,5-Triazinyltetrazoles with Targeted Delivery Molecules to the Targets of Microenvironment Tumor Cells”).

No human or animal subjects were used in this research.

The authors declare no competing interests.

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Mikolaichuk, O.V., Sharoyko, V.V., Popova, E.A. et al. A new tetrazole-containing 2-amino-4,6-di(aziridin-1-yl)-1,3,5-triazine derivative: synthesis, interaction with DNA, and antitumor activity. Russ Chem Bull 71, 1050–1056 (2022). https://doi.org/10.1007/s11172-022-3507-1

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