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Synthesis and studies of biological activity of N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines as potential multifunctional agents for treatment of neurodegenerative diseases

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Abstract

A number of N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines with different substituents at position 5 of thiazoline ring was synthesized and their inhibitory activity against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), horse serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was studied, as well as their antioxidant properties in DPPH and ABTS tests (DPPH is the 2,2-diphenyl-1-picrylhydrazyl, ABTS is the 2,2´-azinobis(3-ethylbenzthiazolino-6-sulfonic acid)). All the studied compounds virtually do not inhibit AChE, whereas the inhibition degree of BChE and CaE depends on the substituent structure. The presence of radical-binding activity comparable with the standard antioxidant ascorbic acid was shown for compounds containing a iodomethyl substituent. The found lead compound (R1 = H, R2 = CH2I) combines the antioxidant properties and the ability to efficiently inhibit BChE, simultaneously possessing an optimal esterase profile. The performed studies showed that N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines are a new promising class of compounds, which can be used for the development of multifunctional agents for treatment of neurodegenerative diseases.

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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, N. P. Boltneva, O. G. Serebryakova, E. V. Rudakova, A. N. Proshin & S. O. Bachurin

  2. Department of Chemistry, M. V. Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    T. P. Trofimova

Authors
  1. G. F. Makhaeva
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  2. T. P. Trofimova
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  3. N. P. Boltneva
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  4. O. G. Serebryakova
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  5. E. V. Rudakova
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  6. A. N. Proshin
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  7. S. O. Bachurin
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Correspondence to G. F. Makhaeva.

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Dedicated to Academician of the Russian Academy of Sciences O. G. Sinyashin on the occasion of his 60th birthday.

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1341–1345, May, 2016.

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Makhaeva, G.F., Trofimova, T.P., Boltneva, N.P. et al. Synthesis and studies of biological activity of N-(4-tert-butylbenzyl)-N-(pyridin-3-ylmethyl)-2-aminothiazolines as potential multifunctional agents for treatment of neurodegenerative diseases. Russ Chem Bull 65, 1341–1345 (2016). https://doi.org/10.1007/s11172-016-1459-z

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  • DOI: https://doi.org/10.1007/s11172-016-1459-z

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