Advertisement

Russian Chemical Bulletin

, Volume 67, Issue 11, pp 2121–2126 | Cite as

Aminoadamantane conjugates with carbazole derivatives as potential multitarget agents for the treatment of Alzheimer’s disease. Effect of the spacer structure

  • G. F. Makhaeva
  • E. F. Shevtsova
  • N. V. Kovaleva
  • E. V. Rudakova
  • M. E. Neganova
  • L. G. Dubova
  • P. N. Shevtsov
  • A. Yu. Aksinenko
  • V. B. Sokolov
  • S. O. Bachurin
Full Articles
  • 13 Downloads

Abstract

The paper considers the influence of the structure of aminoadamantane–carbazole conjugates linked by five different spacers on their ability to inhibit acetylcholinesterase, butyrylcholinesterase (BChE), and carboxylesterase, the radical scavenging and mitoprotective activity, and tubulin polymerization. The nature of the spacer was found to be determinant for the appearance of anti-BChE and radical-scavenging activity. Aminoadamantane–carbazole conjugates linked by flexible spacers proved to be most effective in these assays. The influence of the conjugates on mitochondrial functions and tubulin polymerization largely depends on the structure of the carbazole moiety. A series of lead compounds promising for further study was identified as potential drugs for the treatment of neurodegenerative diseases, in particular, Alzheimer’s disease.

Key words

1-aminoadamantanes carbazoles tetrahydrocarbazoles acetylcholinesterase butyrylcholinesterase carboxylesterase antioxidants conjugates mitoprotective agents tubulin microtubules 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Y. Huang, L. Mucke, Cell, 2012, 148, 1204; DOI: 10.1016/j. cell.2012.02.040.CrossRefGoogle Scholar
  2. 2.
    M. L. Bolognesi, A. Cavalli, ChemMedChem, 2016, 11, 1190; DOI: 10.1002/cmdc.201600161.CrossRefGoogle Scholar
  3. 3.
    M. Carreiras, E. Mendes, M. Perry, A. Francisco, J. Marco-Contelles, Curr. Top. Med. Chem., 2013, 13, 1745; DOI: 10.2174/15680266113139990135.CrossRefGoogle Scholar
  4. 4.
    E. F. Shevtsova, D. V. Vinogradova, M. E. Neganova, M. Avila-Rodriguez, G. M. Ashraf, G. E. Barreto, S. O. Bachurin, G. Aliev, CNS Neurol. Disord. Drug Targets, 2017, 16, 677; DOI: 10.2174/1871527316666170424114444.CrossRefGoogle Scholar
  5. 5.
    N. Lermontova, N. Lukoyanov, T. Serkova, E. Lukoyanova, S. Bachurin, Mol. Chem. Neuropathol., 1998, 33, 51; DOI: 10.1007/bf02815859.CrossRefGoogle Scholar
  6. 6.
    H. W. Klafki, M. Staufenbiel, J. Kornhuber, J. Wiltfang, Brain, 2006, 129, 2840; DOI: 10.1093/brain/awl280.CrossRefGoogle Scholar
  7. 7.
    J. Rodda, J. Carter, BMJj, 2012, 344, e2986; DOI: 10.1136/bmj.e2986.Google Scholar
  8. 8.
    F. Mangialasche, A. Solomon, B. Winblad, P. Mecocci, M. Kivipelto, Lancet Neurol., 2010, 9, 702; DOI: 10.1016/S1474-4422(10)70119-8.CrossRefGoogle Scholar
  9. 9.
    M. Rosini, E. Simoni, A. Minarini, C. Melchiorre, Neurochem. Res., 2014, 39, 1914; DOI: 10.1007/s11064-014-1250-1.CrossRefGoogle Scholar
  10. 10.
    A. Agis-Torres, M. Solhuber, M. Fernandez, J. M. Sanchez-Montero, Curr. Neuropharmacol., 2014, 12, 2; DOI: 10.2174/1570159X113116660047.CrossRefGoogle Scholar
  11. 11.
    S. O. Bachurin, E. V. Bovina, A. A. Ustyugov, Med. Res. Rev., 2017, 37, 1186; DOI: 10.1002/med.21434.CrossRefGoogle Scholar
  12. 12.
    S. O. Bachurin, E. F. Shevtsova, G. F. Makhaeva, V. V. Grigoriev, N. P. Boltneva, N. V. Kovaleva, S. V. Lushchekina, P. N. Shevtsov, M. E. Neganova, O. M. Redkozubova, E. V. Bovina, A. V. Gabrelyan, V. P. Fisenko, V. B. Sokolov, A. Y. Aksinenko, V. Echeverria, G. E. Barreto, G. Aliev, Sci. Rep., 2017, 7, 45627; DOI: 10.1038/srep45627.CrossRefGoogle Scholar
  13. 13.
    G. F. Makhaeva, V. B. Sokolov, E. F. Shevtsova, N. V. Kovaleva, S. V. Lushchekina, N. P. Boltneva, E. V. Rudakova, A. Y. Aksinenko, P. N. Shevtsov, M. E. Neganova, L. G. Dubova, S. O. Bachurin, Pure Appl. Chem., 2017, 89; DOI: 10.1515/pac-2017-0308.Google Scholar
  14. 14.
    S. O. Bachurin, Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova, 2016, 116, 77; DOI: 10.17116/jnevro20161168177-87.CrossRefGoogle Scholar
  15. 15.
    A. Cavalli, M. L. Bolognesi, A. Minarini, M. Rosini, V. Tumiatti, M. Recanatini, C. Melchiorre, J. Med. Chem., 2008, 51, 347; DOI: 10.1021/jm7009364.CrossRefGoogle Scholar
  16. 16.
    V. B. Sokolov, A. Y. Aksinenko, T. V. Goreva, T. A. Epishina, V. V. Grigor’ev, A. V. Gabrel’yan, D. V. Vinogradova, M. E. Neganova, E. F. Shevtsova, S. O. Bachurin, Russ. Chem. Bull., 2016, 65, 1354; DOI: 10.1007/s11172-016-1461-5.CrossRefGoogle Scholar
  17. 17.
    V. B. Sokolov, A. Y. Aksinenko, T. A. Epishina, T. V. Goreva, S. O. Bachurin, Russ. Chem. Bull., 2017, 66, 2110; DOI: 10.1007/s11172-017-1988-0.CrossRefGoogle Scholar
  18. 18.
    S. O. Bachurin, V. B. Sokolov, A. Y. Aksinenko, T. A. Epishina, T. V. Goreva, E. F. Shevtsova, P. N. Shevtsov, Pat. RF 2608631, 2017 (in Russian).Google Scholar
  19. 19.
    A. Nordberg, C. Ballard, R. Bullock, T. Darreh-Shori, M. Somogyi, Prim. Care Companion. CNS Disord., 2013, 15, PCC.12r01412; DOI: 10.4088/PCC.12r01412.Google Scholar
  20. 20.
    G. L. Ellman, K. D. Courtney, V. Andres, M. Feather-Stone, Biochem. Pharmacol., 1961, 7, 88; DOI: 10.1016/0006-2952(61)90145-9.CrossRefGoogle Scholar
  21. 21.
    S. H. Sterri, B. A. Johnsen, F. Fonnum, Biochem. Pharmacol., 1985, 34, 2779; DOI: 10.1016/0006-2952(85)90579-9.CrossRefGoogle Scholar
  22. 22.
    R. Re, N. Pellegrini, A. Proteggente, A. Pannala, M. Yang, C. Rice-Evans, Free Radic. Biol. Med., 1999, 26, 1231; DOI: 10.1016/s0891-5849(98)00315-3.CrossRefGoogle Scholar
  23. 23.
    E. R. Milaeva, D. B. Shpakovsky, Y. A. Gracheva, T. A. Antonenko, D. I. Osolodkin, V. A. Palyulin, P. N. Shevtsov, M. E. Neganova, D. V. Vinogradova, E. F. Shevtsova, J. Organomet. Chem., 2015, 782, 96; DOI: 10.1016/j.jorganchem.2014.12.013.CrossRefGoogle Scholar
  24. 24.
    P. N. Shevtsov, E. F. Shevtsova, G. Burbaeva, Bull. Exp. Biol. Med., 2016, 161, 451; DOI: 10.1007/s10517-016-3436-9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • G. F. Makhaeva
    • 1
  • E. F. Shevtsova
    • 1
  • N. V. Kovaleva
    • 1
  • E. V. Rudakova
    • 1
  • M. E. Neganova
    • 1
  • L. G. Dubova
    • 1
  • P. N. Shevtsov
    • 1
  • A. Yu. Aksinenko
    • 1
  • V. B. Sokolov
    • 1
  • S. O. Bachurin
    • 1
  1. 1.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow RegionRussian Federation

Personalised recommendations