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Synthesis of Betulin Conjugates and Its 1,2,3-Triazole Derivatives

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Abstract

This review summarizes the main methods to introduce a triazole moiety into the structures of a pentacyclic triterpenoid betulin and its derivatives. The prospect of using 1,2,3-triazole-containing triterpenoids as drugs is laid out.

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REFERENCES

  1. B. Meunier, “Hybrid molecules with a dual mode of action: Dream or reality?,” Acc. Chem. Res. 41, 69–77 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. M. Kvasnica, M. Urban, N. J. Dickinson, and J. Sarek, “Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: Synthesis and medicinal significance,” Nat. Prod. Rep. 32, 1303–1330 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. M. Zhou, R.-H. Zhang, M. Wang, G.-B. Xu, S.-G. Liao, “Prodrugs of triterpenoids and their derivatives,” Eur. J. Med. Chem. 131, 222–236 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. L. Borkova, J. Hodon, and M. Urban, “Synthesis of betulinic acid derivatives with modified a-rings and their development as potential drug candidates,” Asian J. Org. Chem. 7, 1542–1560 (2018).

    Article  CAS  Google Scholar 

  5. J. L. C. Sousa, C. S. R. Freire, A. J. D. Silvestre, and A. M. S. Silva, “Recent developments in the functionalization of betulinic acid and its natural analogues: A route to new bioactive compounds,” Molecules 24, 355 (2019).

    Article  PubMed Central  PubMed  Google Scholar 

  6. S. Xiao, Z. Tian, Y. Wang, L. Si, L. Zhang, and D. Zhou, “Recent progress in the antiviral activity and mechanism study of pentacyclic triterpenoids and their derivatives,” Med. Res. Rev. 38, 951–976 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  7. J. Hodon, L. Borkova, J. Pokorny, A. Kazakova, and M. Urban, “Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research,” Eur. J. Med. Chem. 182, 111653–111678 (2019).

    Article  CAS  PubMed  Google Scholar 

  8. V. V. Rostovtsev, L. G. Green, V. V. Fokin, and K. B. Sharpless, “A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective ‘ligation’ of azides and terminal alkynes,” Angew. Chem. Int. Ed. 41, 2596–2599 (2002).

    Article  CAS  Google Scholar 

  9. H. C. Kolb, M. G. Finn, and K. B. Sharpless, “Click Chemistry: Diverse Chemical Function from a Few Good Reactions,” Angew. Chem., Int. Ed. Engl. 40, 2004–2021 (2002).

    Article  Google Scholar 

  10. R. Csuk, A. Barthel, R. Kluge, and D. Strohl, “Synthesis, cytotoxicity and liposome preparation of 28-acetylenic betulin derivatives,” Bioorg. Med. Chem. 18, 7252–7259 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. V. Khwaza, S. Mlala, O. O. Oyedeji, and B. A. Aderibigbe, “Pentacyclic triterpenoids with nitrogen-containing heterocyclic moiety, privileged hybrids in anticancer drug discovery,” Molecules 26, 2401 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. R. Csuk and H. P. Deigner, “The potential of click reactions for the synthesis of bioactive triterpenes,” Bioorg. Med. Chem. Lett. 29, 949–958 (2019).

    Article  CAS  PubMed  Google Scholar 

  13. M. Tomanek, S. Siudak, M. Latocha, and S. Boryczka, “New 30-substituted derivatives of pentacyclic triterpenes: Preparation, biological activity, and molecular docking study,” J. Mol. Struct. 1226, 129394–129404 (2021).

    Article  Google Scholar 

  14. E. Bebenek, M. Kadela-Tomanek, E. Chrobak, M. Jastrzebska, and M. Ksiazek, “Synthesis and structural characterization of a new 1,2,3-triazole derivative of pentacyclic triterpene,” Crystals 12, 422 (2022).

    Article  CAS  Google Scholar 

  15. G. Gonzalez, J. Hodon, A. Kazakova, C. D' Acunto, P. Kanovsky, M. Urban, and M. Strnad, “Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models,” Eur. J. Med. Chem. 213, 113168 (2021).

    Article  CAS  PubMed  Google Scholar 

  16. A. Antimonova, N. Petrenko, M. Shakirov, T. Rybalova, T. Frolova, E. Shults, T. Kukina, O. Sinitsyna, and G. Tolstikov, “Synthesis and study of mutagenic properties of lupane triterpenoids containing 1,2,3-triazole fragments in the C-30 position,” Chem. Nat. Compd 49, 657–664 (2013).

    Article  CAS  Google Scholar 

  17. J. Pokorny, V. Horka, V. Sidova, and M. Urban, “Synthesis and characterization of new conjugates of betulin diacetate and bis(triphenysilyl)betulin with substituted triazoles,” Monatsh. Chem. 149, 839–845 (2018).

    Article  CAS  Google Scholar 

  18. A. P. D. de Souza and S. C. B. Gnoatto, “New triazole triterpene derivative exhibits anti-RSV activity synthesis biological evaluation and molecular modeling,” Beilstein Arch. 202231 (2022).

  19. W. Shi, N. Tang, and W. D. Yan, “Synthesis and cytotoxicity of triterpenoids derived from betulin and betulinic acid via click chemistry,” J. Asian Nat. Prod. Res. 17, 159–169 (2015).

    Article  CAS  PubMed  Google Scholar 

  20. R. Majeed, P. L. Sangwan, P. K. Chinthakindi, I. Khan, N. A. Dangroo, N. Thota, A. Hamid, P. R. Sharma, A. K. Saxena, and S. Koul, “Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents,” Eur. J. Med. Chem. 63, 782–792 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. I. Khan, S. K. Guru, S. K. Rath, P. K. Chinthakindi, B. Singh, S. Koul, S. Bhushan, P. L. Sangwan, “A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells,” Eur. J. Med. Chem. 108, 104–116 (2016).

    Article  CAS  PubMed  Google Scholar 

  22. V. Sidova, P. Zoufaly, J. Pokorny, P. Dzubak, M. Hajduch, I. Popa, and M. Urban, “Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by huisgen cycloaddition from 30-azidoderivatives,” PLOS One 12, 0171621 (2017).

    Article  Google Scholar 

  23. E. Bebenek, M. Jastrzebska, M. Kadela-Tomanek, E. Chrobak, B. Orzechowska, K. Zwolinska, M. Latocha, A. Mertas, Z. Czuba, and S. Boryczka, “Novel triazole hybrids of betulin: Synthesis and biological activity profile,” Molecules 22, 1876 (2017).

    Article  PubMed Central  PubMed  Google Scholar 

  24. E. Bebenek, M. Kadela-Tomanek, E. Chrobak, M. Latocha, and S. Boryczka, “Novel triazoles of 3-acetylbetulin and betulone as anticancer agents,” Med. Chem. Res. 27, 2051–2061 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. T. A. Dang Thi, N. T. Kim Tuyet, C. Pham The, H. Thanh Nguyen, C. Ba Thi, H. Thi Phuong, L. Van Boi, T. Van Nguyen, and M. D’hooghe, “Synthesis and cytotoxic evaluation of novel amide–triazole-linked triterpenoid–AZT conjugates,” Tetrahedron Lett. 56, 218–224 (2015).

    Article  CAS  Google Scholar 

  26. P. Suman, A. Patel, L. Solano, G. Jampana, Z. S. Gardner, C. M. Holt, and S. C. Jonnalagadda, “Synthesis and cytotoxicity of Baylis–Hillman template derived betulinic acid-triazole conjugates,” Tetrahedron 73, 4214–4226 (2017).

    Article  CAS  Google Scholar 

  27. V. V. Grishko, I. A. Tolmacheva, V. O. Nebogatikov, N. V. Galaiko, A. V. Nazarov, M. V. Dmitriev, and I. B. Ivshina, “Preparation of novel ring-a fused azole derivatives of betulin and evaluation of their cytotoxicity,” Eur. J. Med. Chem. 125, 629–639 (2017).

    Article  CAS  PubMed  Google Scholar 

  28. R. Wang, Y. Li, H. Hu, L. Persoons, D. Daelemans, S. Jonghe, W. Luyten, B. Krasniqi, and W. Dehaen, “Antibacterial and antitumoral properties of 1,2,3-triazolo fused triterpenes and their mechanism of inhibiting the proliferation of HL-60 cells,” Eur. J. Med. Chem. 224, 113727 (2021).

    Article  CAS  PubMed  Google Scholar 

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Funding

The work was performed within the framework of a state order, registration no. 122012400109-8.

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Correspondence to M. A. Nazarov.

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The authors declare that they have no conflicts of interest.

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Translated by A. Tulyabaew

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Nazarov, M.A., Polovnikova, A.A. & Tolmacheva, I.A. Synthesis of Betulin Conjugates and Its 1,2,3-Triazole Derivatives. Polym. Sci. Ser. D 16, 543–548 (2023). https://doi.org/10.1134/S199542122303022X

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  • DOI: https://doi.org/10.1134/S199542122303022X

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