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

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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.

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Authors and Affiliations

  1. Institute of Physiologically Active Compounds, Russian Academy of Sciences, 1 Severny proezd, 142432, Chernogolovka, Moscow Region, Russian Federation

    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

Authors
  1. G. F. Makhaeva
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  2. E. F. Shevtsova
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  3. N. V. Kovaleva
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  4. E. V. Rudakova
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  5. M. E. Neganova
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  6. L. G. Dubova
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  7. P. N. Shevtsov
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  8. A. Yu. Aksinenko
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  9. V. B. Sokolov
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  10. S. O. Bachurin
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Corresponding author

Correspondence to G. F. Makhaeva.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2121–2126, November, 2018.

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Makhaeva, G.F., Shevtsova, E.F., Kovaleva, N.V. et al. Aminoadamantane conjugates with carbazole derivatives as potential multitarget agents for the treatment of Alzheimer’s disease. Effect of the spacer structure. Russ Chem Bull 67, 2121–2126 (2018). https://doi.org/10.1007/s11172-018-2338-6

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  • DOI: https://doi.org/10.1007/s11172-018-2338-6

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