Lipoylcarnosine: Synthesis, Study of Physico-Chemical and Antioxidant Properties, Biological Activity

  • S. L. StvolinskyEmail author
  • N. A. Antonova
  • O. I. Kulikova
  • A. V. Lopachev
  • D. A. Abaimov
  • I. Al-Baidani
  • O. M. Lopacheva
  • T. N. Fedorova
  • A. P. Kaplun
  • G. M. Sorokoumova


Synthesis of lipoylcarnosine (LipС), a conjugated molecule based on two natural antioxidants, carnosine and α-lipoic acid, is described and its physico-chemical, antioxidant properties and biological activity are characterized. According to reversed-phase HPLC with a UV detector, purity of the final product was 89.3%. The individuality of the obtained sodium salt of LipС was confirmed by tandem HPLC-mass spectrometry. LipC demonstrated high resistance to hydrolysis with serum carnosinase. The antioxidant activity of LipC evaluated by the reaction with the formation of thiobarbituric acid reacting substances and kinetic parameters of iron-induced chemiluminescence was higher than that of carnosine and lipoic acid. LipC did not affect viability of SH-SY5Y human neuroblastoma cells, differentiated to the dopaminergic phenotype, at concentrations not exceeding 5 mM. In the concentration range of 0.1–0.25 mM LipC protected neuronal cells against 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity.


carnosine α-lipoic acid lipoylcarnosine antioxidant carnosinase parkinsonism 



  1. 1.
    Halliwell, B., Rafter, J., and Jenner, A., Am. J. Clin. Nutr., 2005, vol. 81, pp. 268S–276S.CrossRefGoogle Scholar
  2. 2.
    Rizvi, S.I. and Jha, R., Expert. Opin. Drug. Discov., 2011, vol. 6, pp. 89–102.CrossRefGoogle Scholar
  3. 3.
    Cross, C., Halliwell, B., Borish, E., Pryor, W., Ames, B., Saul, R., McCord, J., and Harman, D., Ann. Intern. Med., 1987, vol. 107, pp. 526–545.CrossRefGoogle Scholar
  4. 4.
    Baldeiras, I., Santana, I., Proença, M.T., Garrucho, M.H., Pascoal, R., Rodrigues, A., Duro, D., and Oliveira, C.R., J. Alzheimer’s Dis., 2010, vol. 21, pp. 1165–1177.CrossRefGoogle Scholar
  5. 5.
    Reuter, S., Gupta, S.C., Chaturvedi, M.M., and Aggarwal, B.B., Free Radic. Biol. Med., 2010, vol. 49, pp. 1603–1616.CrossRefGoogle Scholar
  6. 6.
    Feruzi, O., Miri, R., Tavakkoli, M., and Saso, L., Curr. Med. Chem., 2011, vol. 18, pp. 3871–3888.CrossRefGoogle Scholar
  7. 7.
    Boldyrev, A.A., Biochemistry (Moscow), 2012, vol. 77, pp. 403–418.Google Scholar
  8. 8.
    Boldyrev, A.A., Aldini, G., and Derave, W., Physiol. Rev., 2013, vol. 93, pp. 1803–1845.CrossRefGoogle Scholar
  9. 9.
    Fedorova, T.N., Belyaev, M.S., Trunova, O.A., Gnezditskii, V.V., Maksimova, M.Yu., and Boldyrev, A.A., Biol. Membr. (Moscow), 2008, vol. 25, pp. 479–483.Google Scholar
  10. 10.
    Boldyrev, A., Fedorova, T., Stepanova, M., Dobrotvorskaya, I., Kozlova, E., Boldanova, N., Bagyeva, G., Ivanova-Smolenskaya, I., and Illarioshkin, S., Rejuvenation Res., 2008, vol. 11, pp. 821–827.CrossRefGoogle Scholar
  11. 11.
    Margolis, F.L., Grillo, M., Grannot-Reisfeld, N., and Farbman, I., Biochim. Biophys. Acta, 1983, vol. 744, pp. 237–248.CrossRefGoogle Scholar
  12. 12.
    Stvolinsky, S.L., Bulygina, E.R., Fedorova, T.N., Meguro, K., Sato, T., Tyulina, O.V., Abe, H., and Boldyrev, A.A., Cell. Mol. Neurobiol., 2010, vol. 30, pp. 395–404.CrossRefGoogle Scholar
  13. 13.
    Goraca, A., Huk-Kolega, H., Piechota, A., Kleniewska, P., Ciejka, E., and Skibska, B., Pharmacol. Rep., 2011, vol. 63, pp. 849–858.CrossRefGoogle Scholar
  14. 14.
    Bilska, A. and Wlodek, L., Pharmacol. Rep., 2005, vol. 57, pp. 570–577.Google Scholar
  15. 15.
    Shay, K.P., Morea, R.F., Smith, E.J., Smith, A.R., and Hagen, T.M., Biochim. Biophys. Acta, 2009, vol. 1790, pp. 1149–1160.CrossRefGoogle Scholar
  16. 16.
    Anti-Aging Complex (ALA/ALC/Carnosine/GSE). Ray & Terry’s Longevity Products © Copyright Ray and Terry’s Health Products Inc. All Rights Reserved, 2011. Scholar
  17. 17.
    Giampapa, V., US Patent 20060269617 A1, 2006.Google Scholar
  18. 18.
    Guasti, P.L., US Patent 20120129781 Al, 2013.Google Scholar
  19. 19.
    Nativi, C., Ghelardini, C., Giancarlo La, M., and Dragoni, E. US Patent 20130072533A1, 2013.Google Scholar
  20. 20.
    Nativi, C., Gualdani, R., Dragoni, E., Di CesareMannelli, L., Sostegni, S., Norcini, M., Gabrielli, G., la Marca, G., Richichi, B., Francesconi, O., Moncelli, M.R., Ghelardini, C., and Roelens, S. Sci. Reports, 2013, vol. 3. doi 10.1038/srep02005Google Scholar
  21. 21.
    Antonova, N.A., Sorokoumova, G.M., Fedorova, T.N., Stvolinsky, S.L., Abaimov, D.A., Popenko, V.I., and Shvets, V.I., Tonkie Khimicheskie Tekhnologii, 2016, vol. 11, no. 6, pp. 55–62.Google Scholar
  22. 22.
    Pegova, A., Abe, H., and Boldyrev, A., Comp. Biochem. Physiol., part B, Biochem. Mol. Biol., 2000, vol. 127, pp. 443–446.CrossRefGoogle Scholar
  23. 23.
    Presgraves, S.P., Ahmed, T., Borwege, S., and Joyce, J.N., Neurotox. Res., 2004, vol. 5, pp. 579–598.CrossRefGoogle Scholar
  24. 24.
    Pahlman, S., Ruusala, A.I., Abrahamsson, L., Mattsson, M.E., and Esscher, T., Cell Differ., 1984, vol. 14, pp. 135–144.CrossRefGoogle Scholar
  25. 25.
    Scudiero, D.A., Shoemaker, R.H., Paull, K.D., Monks, A., Tierney, S., Nofziger, T.H., Currens, M.J., Seniff, D., and Boyd, M.R., Cancer Res., 1988, vol. 48, pp. 4827–4833.Google Scholar
  26. 26.
    Sorokoumova, G.M., Selishcheva, A.A., and Kaplun, A.P., Fosfolipidy: Metody ikh vydeleniya, obnaruzheniya i izucheniya fiziko-khimicheskikh svoistv lipidnykh dispersyi v vode. Uchebnoe posobie po bioorganicheskoi khimii (Phospholipids: Methods of Their Isolation, Detection and Analysis of Physico-Chemical Lipid Dispersions in Water. A Handbook of Bioorganic Chemistry), Moscow: Moscow Technological University, 2001.Google Scholar
  27. 27.
    Fedorova, T.N., Eksper. Klin. Farmakol., 2003, vol. 66, no. 5, pp. 56–58.Google Scholar
  28. 28.
    Bellia, F., Vecchio, G., and Rizzarelli, E., Molecules, 2014, vol. 19, pp. 2299–2329.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • S. L. Stvolinsky
    • 1
    Email author
  • N. A. Antonova
    • 2
  • O. I. Kulikova
    • 1
    • 3
  • A. V. Lopachev
    • 1
  • D. A. Abaimov
    • 1
  • I. Al-Baidani
    • 2
  • O. M. Lopacheva
    • 1
    • 4
  • T. N. Fedorova
    • 1
  • A. P. Kaplun
    • 2
  • G. M. Sorokoumova
    • 2
  1. 1.Research Center of NeurologyMoscowRussia
  2. 2.Moscow Technological UniversityMoscowRussia
  3. 3.Peoples’ Friendship University of RussiaMoscowRussia
  4. 4.Moscow State University, International Biotechnological CenterMoscowRussia

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