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Synthesis of new N-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases

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Abstract

New N-(pyridin-3-ylmethyl)-2-aminothiazolines containing various substituents at the 5 position of the thiazoline ring and the 4-tert-butylbenzyl, 4-isopropylbenzyl, or 4-fluorobenzyl moiety at the nitrogen atom of the amino group were synthesized. The inhibitory activity of the synthesized compounds against human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), equine serum butyrylcholinesterase (BChE, EC 3.1.1.8), and porcine liver carboxylesterase (CaE, EC 3.1.1.1) was evaluated and their antioxidant properties were studied by ABTS assay. N-(Pyridin-3-ylmethyl)-2-aminothiazolines proveded to be very weak AChE inhibitors, while their inhibitory activity against BChE and CaE was structure-dependent. 2-Aminothiazolines containing the 4-tert-butylbenzyl moiety are more efficient BChE inhibitors compared to the derivatives containing the 4-isopropylbenzyl or 4-fluorobenzyl substituent. An analysis of the dependence of the esterase profile of N-(pyridin-3-ylmethyl)-2-aminothiazolines on the structure of the substituent at the 5 position of the thiazoline ring of these compounds demonstrated that the derivatives containing the iodomethyl substituent possess the highest anti-BChE activity, the compounds with R2 = H and R3 = CH2I have the optimal esterase profile. Regardless of the structure of the substituents in the benzyl moiety, all N-(pyridin-3-ylmethyl)-2-aminothiazolines containing the iodomethyl substituent at the 5 position of the thiazoline ring exhibited high radical scavenging activity comparable with that of the standard antioxidant Trolox. N-(Pyridin-3-ylmethyl)-2-aminothiazolines were shown to be a new promising class of compounds for the design of multifunctional agents for the treatment of neurodegenerative diseases.

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Authors and Affiliations

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

    G. F. Makhaeva, N. P. Boltneva, E. V. Rudakova, O. G. Serebryakova, A. N. Proshin & S. O. Bachurina

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

    T. P. Trofimova

  3. N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Science, 4 ul. Kosygina, 119334, Moscow, Russian Federation

    S. V. Lushchekina

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  1. G. F. Makhaeva
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  2. T. P. Trofimova
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Correspondence to G. F. Makhaeva.

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Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1897—1904, October, 2017.

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Makhaeva, G.F., Trofimova, T.P., Boltneva, N.P. et al. Synthesis of new N-(pyridin-3-ylmethyl)-2-aminothiazoline derivatives possessing anticholinesterase and antiradical activity as potential multifunctional agents for the treatment of neurodegenerative diseases. Russ Chem Bull 66, 1897–1904 (2017). https://doi.org/10.1007/s11172-017-1964-8

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