Russian Journal of Bioorganic Chemistry

, Volume 45, Issue 6, pp 545–551 | Cite as

Synthesis and Antimicrobial and Antifungal Activity of Resin Acid Acetylene Derivatives

  • E. V. TretyakovaEmail author
  • E. V. Salimova
  • L. V. Parfenova


A series of diterpenes that contain the morpholine, pyrrolidine, benzyl, nitrophenyl, and 1,2,3-tetrazole heterocyclic fragments have been synthesized from acetylene derivatives of abietic, 7-formylabietic, dehydroabietic, maleopimaric, and dihydroquinopimaric acids. The antibacterial activity of the synthesized compounds against microorganisms and pathogenic fungi has been studied, and the primary assessment of their cytotoxicity and hemolytic activity has have been carried out. It has been found that the acetylene derivatives of abietic and dehydroabietic acids that contain the pyrrolidine substituent can effectively inhibit the growth of fungi Candida albicans and Cryptococcus neoformans, and their low hemolytic ability has been shown.


diterpenoids abietic acid dehydroabietic acid 7-formylabietic acid maleopimaric acid dihydroquinopimaric acid antibacterial activity, fungicidal activity 



The work was performed as a part of the State assignment (AAAA-A19-119022290012-3) and was supported by the grant no. 17-43-020021 р_а from the Russian Science Foundation. The structural studies of compounds (IV–VII) were performed in the Center of Collective Use Agidel at the Institute of Petrochemistry and Catalysis of the Russian Academy of Sciences. The antimicrobial screening of compounds (II–VI) in the Community for Antimicrobial Drug Discovery (CO-ADD) and supported by the Wellcome Trust (Great Britain) and Queensland University (Australia).


This article does not contain any studies with the use of animals and humans as objects of research.

Conflict of Interest

The authors state that there is no conflict of interests.


  1. 1.
    Magiorakos, A.-P., Srinivasan, A., Carey, R.B., Carmeli, Y., Falagas, M.E., Giske, C.G., Harbarth, S., Hindler, J.F., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D.L., Rice, L.B., Stelling, J., Struelens, M.J., Vatopoulos, A., Weber, J.T., and Monnet, D.L., Clin. Microbiol. Infect., 2012, vol. 18, no. 3, pp. 268–281.CrossRefGoogle Scholar
  2. 2.
    Newman, D.J., Cragg, G.M., and Snader, K.M., J. Nat. Prod., 2003, vol. 66, pp. 1022–1037.CrossRefGoogle Scholar
  3. 3.
    Tolstikov, G.A., Tolstikova, T.G., Shul’ts, E.E., Tolstikov, S.E., and Khvostov, M.V., Smolyanye kisloty khvoinykh Rossii. Khimiya, farmakologiya (Resin Acids of Conifers of Russia: Chemistry and Pharmacology), Novosibirsk: GEO, 2011.Google Scholar
  4. 4.
    Xu, H.T., Liu, L.L., Fan, X.T., Zhang, G.J., Li, Y.C., and Jiang, B., Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 505–510.CrossRefGoogle Scholar
  5. 5.
    Huang, X.-Ch., Wang, M., Pan, Y.-M., Yao, G.-Y., and Zhang, Y., Eur. J. Med. Chem., 2013, vol. 69, pp. 508–520.CrossRefGoogle Scholar
  6. 6.
    González, M.A., Correa-Royero, J., Agudelo, L., Mesa, A., and Betancur-Galvis, L., Eur. J. Med. Chem., 2009, vol. 44, pp. 2468–2472.CrossRefGoogle Scholar
  7. 7.
    Hou, W., Luo, Zh., Zhang, G., Cao, D., Li, D., Ruan, H., Ruan, B.H., Su, L., and Xu, H., Eur. J. Med. Chem., 2017, vol. 138, pp. 1042–1052.CrossRefGoogle Scholar
  8. 8.
    Olmo, F., Guardia, J.J., Marin, C., Messouri, I., Rosales, M.J., Urbanova, K., Chayboun, I., Chahboun, R., Alvarez-Manzaneda, E.J., and Sánchez-Moreno, M., Eur. J. Med. Chem., 2015, vol. 89, pp. 683–690.CrossRefGoogle Scholar
  9. 9.
    Pertino, M.W., Vega, C., Rolon, M., Coronel, C., De Arias, A.R., and Schmeda-Hirschmann, G., Molecules, 2017, vol. 22, pp. 369–379.CrossRefGoogle Scholar
  10. 10.
    Zhang, W.M., Yang, T., Pan, X.Y., Liu, X.L., Lin, H.X., Gao, Z.B., Yang, C.G., and Cui, Y.M., Eur. J. Med. Chem., 2017, vol. 127, pp. 917–927.CrossRefGoogle Scholar
  11. 11.
    Berger, M., Roller, A., and Maulide, N., Eur. J. Med. Chem., 2017, vol. 126, no. 27, pp. 937–943.CrossRefGoogle Scholar
  12. 12.
    Helfenstein, A., Vahermo, M., Nawrot, D.A., Demirci, F., Iscan, G., Krogerus, S., Yli-Kauhaluoma, J., Moreira, V.M., and Tammela, P., Bioorg. Med. Chem., 2017, vol. 25, pp. 132–137.CrossRefGoogle Scholar
  13. 13.
    Hou, W., Zhang, G., Luo, Zh., Li, D., Ruan, H., Ruan, B.H., Su, L., and Xu, H., Bioorg. Med. Chem. Lett., 2017, vol. 27, pp. 5382–5386.CrossRefGoogle Scholar
  14. 14.
    14. Caetano da Silva, S.D., Mendes de Souza, M.G., Oliveira Cardoso, M J., da Silva Moraes, T., Ambrósio, S.R., Sola Veneziani, R.C., and Martins, C.H.G., Anaerobe, 2014, vol. 30, pp. 146–152.CrossRefGoogle Scholar
  15. 15.
    Chen, N., Duan, W., Lin, G., Liu, L., Rui, Z., and Li, D., Mol. Divers., 2016, vol. 20, pp. 897–905.CrossRefGoogle Scholar
  16. 16.
    Manner, S., Vahermo, M., Skogman, M.E., Krogerus, S., Vuorela, P.M., Yli-Kauhaluoma, J., Fallarero, A., and Moreira, V.M., Eur. J. Med. Chem., 2015, vol. 102, pp. 68–79.CrossRefGoogle Scholar
  17. 17.
    Tret’yakova, E.V., Zakirova, G.F., Salimova, E.V., Kukovinets, O.S., Odinokov, V.N., and Parfenova, L.V., Med. Chem. Res., 2018, vol. 27, pp. 2199–2213.CrossRefGoogle Scholar
  18. 18.
    Kovaleva, K.S., Yarovaya, O.I., Shernyukov, A.V., Zarubaev, V.V., Shtro, A.A., Orshanskaya, Ya.R., and Salakhutdinov, N.F., Khim. Geterotsikl. Soed., 2017, vol. 53, pp. 364–370.Google Scholar
  19. 19.
    Manner, S., Vahermo, M., Skogman, M.E., Krogerus, S., Vuorela, P.M., Yli-Kauhaluoma, J., Fallarero, A., and Moreira, V.M., Eur. J. Med. Chem., 2015, vol. 102, pp. 68–79.CrossRefGoogle Scholar
  20. 20.
    Aranda, F.J. and Villalain, J., Biochim. Biophys. Acta, 1997, vol. 1327, pp. 171–180.CrossRefGoogle Scholar
  21. 21.
    Ganewatta, M.S., Miller, K.P., Singleton, S.P., Mehrpouya-Bahrami, P., Chen, Y.P., Yan, Y., Nagarkatti, M., Nagarkatti, P., Decho, A.W., and Tang, C., Biomacromolecules, 2015, vol. 16, pp. 3336–3344.CrossRefGoogle Scholar
  22. 22.
    Gonzalez, M.A., Eur. J. Med. Chem., 2014, vol. 87, pp. 834–842.CrossRefGoogle Scholar
  23. 23.
    Sekido, H., Takezawa, J.-I., Motoki, G., and Akatsuka, T., Agric. Biol. Chem., 1990, vol. 54, pp. 287–290.Google Scholar
  24. 24.
    Tretyakova, E.V., Smirnova, I.E., Salimova, E.V., and Odinokov, V.N., Bioorg. Med. Chem., 2015, vol. 23, pp. 6543–6550.CrossRefGoogle Scholar
  25. 25.
    Tret’yakova, E.V., Smirnova, I.E., Salimova, E.V., Pashkova, T.M., Kartashova, O.L., Odinokov, V.N., and Parfenova, L.V., Russ. J. Bioorg. Chem., 2017, vol. 43, no. 3, pp. 317–322.CrossRefGoogle Scholar
  26. 26.
    Tret’yakova, E.V., Salimova, E.V., and Parfenova, L.V., Russ. J. Bioorg. Chem., 2018, vol. 44, no 5, pp. 547–552.CrossRefGoogle Scholar
  27. 27.
    Tret’yakova, E.V., Salimova, E.V., Parfenova, L.V., and Odinokov, V.N., Russ. J. Org. Chem., 2016, vol. 52, no. 10, pp. 1496–1502.CrossRefGoogle Scholar
  28. 28.
    Tret’yakova, E.V., Salimova, E.V., Shakurova, E.R., Parfenova, L.V., and Odinokov, V.N., Russ. J. Org. Chem., 2017, vol. 53, no. 11, pp. 1701–1704.CrossRefGoogle Scholar
  29. 29.
    Nong, W., Chen, X., Liang, J., Wang, L., Tong, Zh., Huang, K., Wu, R., Xie, Q., Jia, Y., and Li, K., Adv. Mat. Res., 2014, vols. 887–888, pp. 551–556.Google Scholar
  30. 30.
    Zalkov, L.U., Ford, R.A., and Cutney, J.P., Org. Chem., 1962, vol. 27, pp. 3535–3539.CrossRefGoogle Scholar
  31. 31.
    Herz, W., Blackstone, R.C., and Nair, M.G., Org. Chem., 1967, vol. 32, pp. 2992–2998.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • E. V. Tretyakova
    • 1
    Email author
  • E. V. Salimova
    • 1
  • L. V. Parfenova
    • 1
  1. 1.Institute of Petrochemistry and Catalysis, Russian Academy of SciencesUfaRussia

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