Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and Study of Some Properties of New Tetrazole-Containing Derivatives of Morpholin-4-yl-1,3,5-triazine and 4-Methylpiperidin-1-yl-1,3,5-triazine

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

Abstract

New tetrazole-containing derivatives of morpholin-4-yl-1,3,5-triazine and 4-methylpiperidin-1-yl-1,3,5-triazine were synthesized. The cytotoxic activity of the obtained compounds against human liver Huh-7 and human lung A549 tumor cell lines was tested by MTT assay. It was demonstrated that these substances do not show pronounced cytotoxic effects. The most significant antitumor activity was exhibited by 1,3,5-triazine containing a 5-phenyltetrazol-2-ylacetohydrazide moiety and a 4-methylpiperidine ring as substituents, as well as by 1,3,5-triazine bearing a 5-methyl-1H-tetrazol-1-ylacetohydrazide moiety and two morpholine rings. For these compounds, the interaction with DNA was studied by UV spectroscopy. Also, for N'-(4,6-dimorpholino-1,3,5-triazin-2-yl)-2-(5-methyl-1H-tetrazol-1-yl)acetohydrazide, the DNA binding constant was determined (Kbin 9.02×104 M−1), and the ability to inhibit the tyrosine kinase domain of the cell-surface receptors was evaluated. It was shown that the studied tetrazole-containing 1,3,5-triazine derivatives do not exhibit antioxidant activity against NO radicals and do not cause photoinduced hemolysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme
Scheme
Scheme
Scheme
Scheme
Scheme
Scheme
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

REFERENCES

  1. Singla, P., Luxami, V., and Paul, K., Eur. J. Med. Chem., 2015, vol. 18, no. 102, p. 39. https://doi.org/10.1016/j.ejmech.2015.07.037

    Article  CAS  Google Scholar 

  2. Cascioferro, S., Parrino, B., Spanò, V., Carbone, A., Montalbano, A., Barraja, P., Diana, P., and Cirrincione, G., Eur. J. Med. Chem., 2017, vol. 15, no. 142, p. 523. https://doi.org/10.1016/j.ejmech.2017.09.035

    Article  CAS  Google Scholar 

  3. Maliszewski, D. and Drozdowska, D., Pharmaceuticals, 2022, vol. 15, no. 2, p. 221. https://doi.org/10.3390/ph15020221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mikolaichuk, O.V., Sharoyko, V.V., Popova, E.A., Protas, A.V., Fonin, A.V., Anufrikov, Y.A., Malkova, A.M., Shmaneva, N.T., Ostrovskii, V.A., Molchanov, O.E., Maistrenko, D.N., and Semenov, K.N., Russ. Chem. Bull., 2022, vol. 71, p. 1050. https://doi.org/10.1007/s11172-022-3507-1

    Article  CAS  Google Scholar 

  5. Konstantinov, S.M. and Berger, M.R., Encyclopedia of Molecular Pharmacology, Berlin: Springer, 2008, p. 53. https://doi.org/10.1007/978-3-540-38918-7_178

  6. Popova, E.A., Trifonov, R.E., and Ostrovskii, V.A., Russ. Chem. Rev., 2019, vol. 88, p. 644. https://doi.org/10.1070/RCR4864

    Article  CAS  Google Scholar 

  7. Ostrovskii, V.A., Trifonov, R.E., and Popova, E.A., Russ. Chem. Bull., 2012, vol. 61, no. 4, p. 768. https://doi.org/10.1007/s11172-012-0108-4

    Article  CAS  Google Scholar 

  8. Ostrovskii, V.A., Popova, E.A., and Trifonov, R.E., in Comprehensive Heterocyclic Chemistry IV, Black, D.St.C., Cossy, J., and Stevens, C.V., Eds., Amsterdam: Elsevier Science, 2022, p. 182. https://doi.org/10.1016/B978-0-12-818655-8.00131-1

  9. Herr, R.J., Bioorg. Med. Chem., 2002, vol. 10, no. 11, p. 3379. https://doi.org/10.1016/S0968-0896(02)00239-0

    Article  CAS  PubMed  Google Scholar 

  10. Patent RU 2124020, Rospatent, 1998, 22 O 393.

  11. Shinichi, Y., Yasuhisa, F., Ichiro, K., Hisashi, Y., Toshiyuki, M., Hiroaki, G., Shuichi, H., Kanami, Y., and Takao, Y., J. Natl. Cancer Inst., 2006, vol. 98, no. 8, p. 545. https://doi.org/10.1093/jnci/djj133

    Article  Google Scholar 

  12. Miller, M.S., Pinson, J.A., Zheng, Z., Jennings, I.G., and Thompson, P.E., Bioorg. Med. Chem. Lett., 2013, vol. 23, no. 3, p. 802-5. https://doi.org/10.1016/j.bmcl.2012.11.076

    Article  CAS  PubMed  Google Scholar 

  13. Norman, M.H., Andrews, K.L., Bo, Y.X.Y., Booker, S.K., Caenepeel, S., Cee, V.J., D’Angelo, N.D., Freeman, D.J., Herberich, B.J., Hong, F.T., Jackson, C.L.M., Jiang, J., Lanman, B.A., Liu, L.B., McCarter, J.D., Mullady, E.L., Nishimura, N., Pettus, L.H., Reed, A.B., Miguel, T.S., Smith, A.L., Stec, M.M., Tadesse, S., Tasker, A., Aidasani, D., Zhu, X.C., Subramanian, R., Tamayo, N.A., Wang, L., Whittington, D.A., Wu, B., Wu, T., Wurz, R.P., Yang, K., Zalameda, L., Zhang, N., and Hughes, P.E., J. Med. Chem., 2012, vol. 55, p. 7796. https://doi.org/10.1021/jm300846z

    Article  CAS  PubMed  Google Scholar 

  14. Dehnhardt, C.M., Venkatesan, A.M., Chen, Z., Delos-Santos, E., Ayral-Kaloustian, S., Brooijmans, N., Yu, K., Hollander, I., Feldberg, L., Lucas, J., and Mallon, R., Bioorg. Med. Chem. Lett., 2011, vol. 16, p. 4773. https://doi.org/10.1016/j.bmcl.2011.06.063

    Article  CAS  Google Scholar 

  15. Mikolaichuk, O.V., Protas, A.V., Popova, E.A., Molchanov, O.E., Maistrenko, D.N., Ostrovskii, V.A., Pavlyukova, Y.N., Sharoyko, V.V., and Semenov, K.N., Russ. J. Gen. Chem., 2022, vol. 92, p. 1621. https://doi.org/10.1134/S1070363222090055

    Article  CAS  Google Scholar 

  16. Sirajuddin, M., Ali, S., and Badshah, A., J. Photochem. Photobiol., B, 2013, vol. 124, p. 1. https://doi.org/10.1016/j.jphotobiol.2013.03.013

    Article  CAS  PubMed  Google Scholar 

  17. Mikolaichuk, O.V., Protas, A.V., Popova, E.A., Mukhametshina, A.V., Ovsepyan, G.K., and Trifonov, R.E., Russ. Chem. Bull., 2018, vol. 67, p. 1312. https://doi.org/10.1007/s11172-018-2217-1

    Article  CAS  Google Scholar 

  18. Topală, T., Bodoki, A., Oprean, L., and Oprean, R., Farmacia, 2014, vol. 62, p. 1049.

    Google Scholar 

  19. García-Ramos, J.C., Galindo-Murillo, R., CortésGuzmán, F., and Azuara, L.R., J. Mex. Chem. Soc., 2013, vol. 57, no. 3, p. 245. https://doi.org/10.29356/jmcs.v57i3.213

    Article  Google Scholar 

  20. Wolfe, A., Shimer, G.H.Jr., and Meehan, Biochemistry, 1987, vol. 26, p. 6392.

    Article  CAS  PubMed  Google Scholar 

  21. Raghu, M.S., Pradeep Kumar, C.B., Prashanth, M.K., Yogesh Kumar, K., Prathibha, B.S., Kanthimathi, G., Alissa, S.A., Alghulikah, H.A., and Osman, S.M., New J. Chem., 2021, vol. 45, p. 13909. https://doi.org/10.1039/D1NJ02419A

    Article  CAS  Google Scholar 

  22. Mikolaichuk, O.V., Popova, E.A., Protas, A.V., Rakipov, I.T., Nerukh, D.A., Petrov, A.V., Charykov, N.A., Ageev, S.V., Tochilnikov, G.V., Zmitrichenko, I.G., Stukov, A.N., Semenov, K.N, and Sharoyko, V.V., J. Mol. Liq., 2022, vol. 356, Art. no. 119043. https://doi.org/10.1016/j.molliq.2022.119043

  23. Laemmli, U.K., Nature, 1970, vol. 227, no. 5259, p. 680. https://doi.org/10.1038/227680a0

    Article  CAS  PubMed  Google Scholar 

  24. Abdelhalim, A.O.E., Sharoyko, V.V., Meshcheriakov, A.A., Martynova, S.D., Ageev, S.V., Iurev, G.O., Al Mulla, H., Petrov, A.V., Solovtsova, I.L., Vasina, L.V., Murin, I.V., and Semenov, K.N., Nanomed. Nanotechnol. Biol. Med., 2020, vol. 29, p. 102284. https://doi.org/10.1016/j.nano.2020.102284

    Article  CAS  Google Scholar 

  25. Gaponenko, I.N., Ageev, S.V., Iurev, G.O., Shemchuk, O.S., Meshcheriakov, A.A., Petrov, A.V., Solovtsova, I.L., Vasina, L.V., Tennikova, T.B., Murin, I.V., Semenov, K.N., and Sharoyko, V.V., Toxicol. in Vitro, 2020, vol. 62, p. 104683. https://doi.org/10.1016/j.tiv.2019.104683

    Article  CAS  PubMed  Google Scholar 

  26. Galebskaya, L.V., Solovtsova, I.L., Miroshnikova, E.B., Mikhailova, I.A., Sushkin, M.E., Razumny, A.V., Babina, A.V., and Fomina, V.A., Biomed. Photonics, 2017, vol. 6, no. 3, p. 33. https://doi.org/10.24931/2413-9432-2017-6-3-33-38

    Article  Google Scholar 

Download references

ACKNOWLEDGMENTS

We are grateful to the “Magnetic Resonance Research Methods”, “Matter Content Analysis Methods”, and “X-ray Diffraction Research Methods” Resource Centers, St. Petersburg State University.

Funding

This study was financially supported by the Ministry of Health of the Russian Federation (State task on the topic “Creation and Evaluation of the Antitumor Activity of Conjugates of Non-Annulated 1,3,5-Triazinyl-Tetrazoles with Targeted Delivery Molecules to Microenvironment Tumor Cells Targets”).

Author information

Authors and Affiliations

  1. Pavlov First St. Petersburg State Medical University, 197022, St. Petersburg, Russia

    O. V. Mikolaichuk, A. V. Protas, E. A. Popova, M. D. Lutsev, V. A. Golotin, K. N. Semenov & V. V. Sharoyko

  2. Granov Russian Research Center for Radiology and Surgical Technologies, Ministry of Health of the Russian Federation, 197758, St. Petersburg, Russia

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

  3. St. Petersburg Branch of “VNIRO” (“GosNOIRH” named after L.S. Berg), 199004, St. Petersburg, Russia

    E. Yu. Smirnov & V. A. Golotin

  4. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    E. Yu. Smirnov

  5. St. Petersburg State Institute of Technology (Technical University), 190013, St. Petersburg, Russia

    V. A. Ostrovskii & K. N. Semenov

  6. St. Petersburg State University, 199034, St. Petersburg, Russia

    I. V. Kornyakov, K. N. Semenov & V. V. Sharoyko

Authors
  1. O. V. Mikolaichuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Protas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. A. Popova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. D. Lutsev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Yu. Smirnov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. A. Golotin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. A. Ostrovskii
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. V. Kornyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. N. Semenov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. V. V. Sharoyko
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. O. E. Molchanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. D. N. Maistrenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. V. Mikolaichuk.

Ethics declarations

No conflict of interest was declared by the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mikolaichuk, O.V., Protas, A.V., Popova, E.A. et al. Synthesis and Study of Some Properties of New Tetrazole-Containing Derivatives of Morpholin-4-yl-1,3,5-triazine and 4-Methylpiperidin-1-yl-1,3,5-triazine. Russ J Gen Chem 93, 1050–1063 (2023). https://doi.org/10.1134/S1070363223050055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363223050055

Keywords:

Search

Navigation