Nootropic Activity of a Novel (-)-Cytisine Derivative (3aR,4S,8S,12R, 12aS,12bR)-10-Methyl-2-Phenyloctahydro-1H-4,12a-Etheno-8,12-Methanopyrrolo[3’,4’:3,4]Pyrido[1,2-a] [1,5]Diazocine-1,3,5(4H)-Trione
- Autores: Makara N.1, Sapozhnikova T.1, Khisamutdinova R.1, Tsypysheva I.1, Borisevich S.1, Kovalskaya A.1, Petrova P.1, Khursan C1, Zarudii F.1,2
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Afiliações:
- Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
- Department of Pharmacology No. 1, Bashkir State Medical University, Ministry of Health of the Russian Federation
- Edição: Volume 164, Nº 4 (2018)
- Páginas: 434-438
- Seção: Pharmacology and Toxicology
- URL: https://journals.rcsi.science/0007-4888/article/view/239670
- DOI: https://doi.org/10.1007/s10517-018-4006-0
- ID: 239670
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Resumo
We performed screening of nootropic properties of 10 new derivatives of quinolizidine alkaloid (-)-cytisine. Compounds with β-endo stereochemistry were more active than α-endo-isomers. Under stress conditions (3aR,4S,8S,12R,12aS,12bR)-10-methyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3’,4’:3,4]pyrido[1,2-a] [1,5]diazocine-1,3,5(4H)-trione enhanced memory and had a positive effect on cognitive functions of rats. According to molecular docking data, the nootropic activity of the compound can be associated with its affinity for the glutamate-binding subunits GluK1 and GluR2 of the kainate and AMPA receptor, respectively.
Sobre autores
N. Makara
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Autor responsável pela correspondência
Email: newpharm@anrb.ru
Rússia, Ufa
T. Sapozhnikova
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
R. Khisamutdinova
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
I. Tsypysheva
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
S. Borisevich
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
A. Kovalskaya
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
P. Petrova
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
C Khursan
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences
Email: newpharm@anrb.ru
Rússia, Ufa
F. Zarudii
Laboratory of Bioorganic Chemistry and Catalysis, Ufa Institute of Chemistry, Russian Academy of Sciences; Department of Pharmacology No. 1, Bashkir State Medical University, Ministry of Health of the Russian Federation
Email: newpharm@anrb.ru
Rússia, Ufa; Ufa