CYTOTOXIC ACTIVITY OF HETEROCYCLIC DERIVATIVES OF BETULIN

Authors

  • N.V. Galaiko Institute of Technical Chemistry of Ural Branch of the RAS

DOI:

Keywords:

triterpenoids, betulin, 1,2,3-triazole, isoxazole, cytotoxic activity

Abstract

In order to obtain active cytotoxic agents, semisynthetic triterpene oxazoles and isoxazoles with a yield of novel heterocyclic azoles with the hydroxyl group at position C (1) or (3) have been modified. A method for synthesis on the basis of betulin modified on carbon (28) azoles has been developed. The screening of anti-tumor activity of the synthesis products has been done, the most promising compounds (IC50 1.6-32.5 mg/ml) being selected.

Supporting Agencies
Работа выполнена при финансовой поддержке грантов программы Президиума РАН (№ 15-21-3-2) и «УМНИК» 2-15-4, код договора 0011452.

Author Biography

  • N.V. Galaiko, Institute of Technical Chemistry of Ural Branch of the RAS
    кандидат химических наук, научный сотрудник, Институт технической химии УрО РАН (ИТХ УрО РАН), 614013, г. Пермь, ул. Академика Королева, 3; e-mail: natagalaiko@gmail.com

References

  1. Terpenoidy rada lupana kak perspektivnye dla mediciny biologiceski aktivnye agenty. C. 2. Polusinteticeskie proizvodnye lupana. Obzor / G.A. Tolstikov, O.B. Flehter, E.E. Sul’c, L.A. Baltina, A.G. Tolstikov // Himia v interesah ustojcivogo razvitia. - 2005. - T. 13. - S. 1-30.
  2. Terpenoidy rada lupana - biologiceskaa aktivnost’ i farmakologiceskie perspektivy. II. Polusinteticeskie proizvodnye lupana / T.G. Tolstikova, I.V. Sorokina, G.A. Tolstikov, A.G. Tolstikov, O.B. Flehter // Bioorganiceskaa himia. - 2006. - T. 32. - S. 291-307.
  3. Sintez proizvodnyh rastitel’nyh triterpenov i issledovanie ih protivovirusnoj i immunostimuliruusej aktivnosti / A.G. Pokrovskij, O.A. Plasunova, T.N. Il’iceva, O.A. Borisova, N.V. Feduk, N.I. Petrenko, V.Z. Petuhova, E.E. Sul’c, G.A. Tolstikov // Himia v interesah ustojcivogo razvitia. - 2001. - T. 9. - S. 485-491.
  4. New cytotoxic lupane triterpenoids from the twigs of Coussarea paniculata / V.S.P. Chaturvedula, J.K. Schilling, R.K. Johnson, D.G.I. Kingston // J. Nat. Prod. - 2003. - Vol. 66. - P. 419-422.
  5. Cichewicz R.H., Kouzi S.A. Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection // Med. Res. Rev. - 2004. - Vol. 24. - P. 90-114.
  6. Synthesis and biological evaluation of heterocyclic ring-fused betulinic acid derivatives as novel inhibitors of osteoclast differentiation and bone resorption / J. Xu, Z. Li, J. Luo, F. Yang, T. Liu, M. Liu, W.-W. Qiu, J. Tang // J. Med. Chem. - 2012. - Vol. 55 - P. 3122-3134.
  7. Heterocycle-fused lupane triterpenoids inhibit Leishmania donovaniamastigotes / R. Haavikko, A. Nasereddin, N. Sacerdoti-Sierra, D. Kopelyanskiy, S. Alakurtti, M. Tikka, C.L. Jaffe, J. Yli-Kauhaluoma // Med. Chem. Commun. - 2014. - Vol. 5. -P. 445-451.
  8. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis / E. Pisha, H. Chai, I.S. Lee, T.E. Chagwedera, N.R. Farnsworth, G.A. Cordell, C.W.W. Beecher, H.H.S. Fong, A.D. Kinghorn, D.M. Brown, M.C. Wani, M.E. Wall, T.J. Hieken, T.K.D. Gupta, J.M. Pezzuto // Nat. Med. - 1995. - Vol. 1. - P. 1046-1051.
  9. Synthesis and cytotoxic activity of A-ring modified betulinic acid derivatives / Y.-J. You, Y. Kim, N.-H. Nam, B.-Z. Ahn // Bioorg. Med. Chem. Lett. - 2003. - Vol. 13. - P. 3137-3140.
  10. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells / V. Zuco, R. Supino, S.C. Righetti, L. Cleris, E. Marchesi, C. Gambacorti-Passerini, F. Formelli // Cancer Lett. - 2002. - Vol. 175. - P. 17-25.
  11. http://clinicaltrials.gov/show/NCT00346502 [Elektronnyj resurs].
  12. Synthesis and cytotoxic activity of heterocyclic ring-substituted betulinic acid derivatives / V. Kumar, N. Rani, P. Aggarwal, V.K. Sanna, A.T. Singh, M Jaggi., N. Joshi, P.K. Sharma, R. Irchhaiya, A.C. Burman // Bioorg. Med. Chem. Lett. - 2008. - Vol. 18. - P. 5058-5062.
  13. Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid / M. Urban, M. Vlk, P. Dzubak, M. Hajduch, J. Sarek // Bioorg. Med. Chem. - 2012. - Vol. 20. - P. 3666-3674.
  14. Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B / H. Li, H. Zou, L. Gao, T. Liu, F. Yang, J. Li, J. Li, W.W. Qiu, J. Tanga // Heterocycles. - 2012. - Vol. 85. - P. 1117-1139.
  15. Synthesis of triterpenoid triazine derivatives from allobetulone and betulonic acid with biological activities / T.D. Ngoc, N. Moons, Y. Kim, W.D. Borggraeve, A. Mashentseva, G. Andrei, R. Snoeck, J. Balzarini, W. Dehaen // Bioorg. Med. Chem. - 2014. - Vol. 22. - P. 3292-3300.
  16. Synthesis, transformation and biological evaluation of 2,3-secotriterpene acetylhydrazones and their derivatives / V.V. Grishko, I.A. Tolmacheva, N.V. Galaiko, A.V. Pereslavceva, L.V. Anikina, L.V. Volkova, B.A. Bachmetyev, P.A. Slepukhin // Eur. J. Med. Chem. - 2013.- Vol. 68. - P. 203-211.
  17. Synthesis of triterpene A-condensed azoles / N.V. Galaiko, A.V. Nazarov, I.A. Tolmacheva, P.A. Slepukhin, Yu.B. Vikharev, O.A. Maiorova, V.V. Grishko // Chem. Het. Compd. - 2014. - Vol. 50. - P. 65-75.
  18. Chemical conversions of betulone produced by biotransformation / V.V. Grishko, A.V. Nazarov, I.A. Tolmacheva, E.V. Tarasova, I.B. Ivshina // Chem. Nat. Compd. - 2014. - Vol. 50. - P. 857-861.

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Published

2015-10-14

Issue

No. 2 (2015)

Section

Research: theory and experiment

How to Cite

Galaiko, N. . (2015). CYTOTOXIC ACTIVITY OF HETEROCYCLIC DERIVATIVES OF BETULIN. Perm Federal Research Centre Journal, 2, 20-23. https://journal.permsc.ru/index.php/pscj/article/view/PSCJ2015n2p4