Influence of the γ-carboline and carbazole pharmacophore moieties on anticholinesterase and antiradical activity of multifunctional agents for the treatment of neurodegenerative diseases
- Авторы: Makhaeva G.1, Boltneva N.1, Kovaleva N.1,2, Rudakova E.1, Lushchekina S.3, Aksinenko A.1, Sokolov V.1
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Учреждения:
- Institute of Physiologically Active Compounds, Russian Academy of Sciences
- Institute of Problems of Chemical Physics, Russian Academy of Sciences
- N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Science
- Выпуск: Том 67, № 9 (2018)
- Страницы: 1724-1731
- Раздел: Article
- URL: https://journals.rcsi.science/1066-5285/article/view/243037
- DOI: https://doi.org/10.1007/s11172-018-2282-5
- ID: 243037
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Аннотация
A comparative analysis of the esterase profile and antiradical activity of two groups of hybrid compounds, viz., tetrahydro-γ-carboline conjugates with carbazoles and tetrahydrocarbazoles (I) and carbazole conjugates with carbazoles and tetrahydrocarbazoles (II), was performed. The replacement of the tetrahydro-γ-carboline moiety (conjugates I) by the carbazole group (conjugates II) was shown to significantly reduce the ability of the compounds to inhibit butyrylcholinesterase (BChE) and scavenge free radicals. The tetrahydro-γ-carboline–tetrahydrocarbazole combination is optimal in terms of both high anti-BChE activity and free radical scavenging ability. According to molecular modeling calculations, the stronger binding of tetrahydro-γ-carboline conjugates (I) in the BChE active site compared to carbazole conjugates (II) is attributed to the ability of I to form ionic and π-cation interactions with amino acid residues lining the BChE gorge. Therefore, conjugates of tetrahydro-γ-carboline and tetrahydrocarbazole derivatives are the most promising compounds for the design of new multitarget drugs combining cognitive-stimulating and antioxidant properties.
Об авторах
G. Makhaeva
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Автор, ответственный за переписку.
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
N. Boltneva
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
N. Kovaleva
Institute of Physiologically Active Compounds, Russian Academy of Sciences; Institute of Problems of Chemical Physics, Russian Academy of Sciences
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432; 1 prosp. Akad. Semenova, Chernogolovka, Moscow Region, 142432
E. Rudakova
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
S. Lushchekina
N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Science
Email: gmakh@ipac.ac.ru
Россия, 4 ul. Kosygina, Moscow, 119334
A. Aksinenko
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432
V. Sokolov
Institute of Physiologically Active Compounds, Russian Academy of Sciences
Email: gmakh@ipac.ac.ru
Россия, 1 Severnyi proezd, Chernogolovka, Moscow Region, 142432