Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases
Bachurin S. O., Makhaeva G. F., Shevtsova E. F., Boltneva N. P., Kovaleva N. V., Lushchekina S. V., Rudakova E. V., Dubova L. G., Vinogradova D. V., Sokolov V. B., Aksinenko A. Y., Fisenko V. P., Richardson R. J., Aliev G.
Scientific Reports
Vol.9, Issue1, Num.4873
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1038/s41598-019-41272-4
Аннотация:
We studied the inhibitory activity of methylene blue (MB) γ-carbolines (gC) conjugates (MB-gCs) against human erythrocyte acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and a structurally related enzyme, porcine liver carboxylesterase (CaE). In addition, we determined the ability of MB-gCs to bind to the peripheral anionic site (PAS) of Electrophorus electricus AChE (EeAChE) and competitively displace propidium iodide from this site. Moreover, we examined the ability of MB-gCs to scavenge free radicals as well as their influence on mitochondrial potential and iron-induced lipid peroxidation. We found that MB-gCs effectively inhibited AChE and BChE with IC 50 values in the range 1.73–10.5 μM and exhibited low potencies against CaE (9.8–26[%] inhibition at 20 μM). Kinetic studies showed that MB-gCs were mixed-type reversible inhibitors of both cholinesterases. Molecular docking results showed that the MB-gCs could bind both to the catalytic active site and to the P
Язык текста: Английский
ISSN: 2045-2322
Bachurin S. O.
Makhaeva G. F.
Shevtsova E. F.
Boltneva N. P.
Kovaleva N. V.
Lushchekina S. V.
Rudakova E. V.
Dubova L. G.
Vinogradova D. V.
Sokolov V. B.
Aksinenko A. Y.
Fisenko V. P. Vladimir Petrovich 1946-
Richardson R. J.
Aliev G. Gyumrakh 1958-
Бачурин С. О.
Махаева Г. Ф.
Шевцова Е. Ф.
Болтнева Н. П.
Ковалева Н. В.
Лушчекина С. В.
Рудакова Е. В.
Дубова Л. Г.
Виноградова Д. В.
Соколов В. Б.
Аксиненко А. Y.
Фисенко В. П. Владимир Петрович 1946-
Ричардсон Р. Й.
Алиев Г. Гюмрах 1958-
Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases
Текст визуальный непосредственный
Scientific Reports
Vol.9, Issue1 Num.4873
2019
Статья
We studied the inhibitory activity of methylene blue (MB) γ-carbolines (gC) conjugates (MB-gCs) against human erythrocyte acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and a structurally related enzyme, porcine liver carboxylesterase (CaE). In addition, we determined the ability of MB-gCs to bind to the peripheral anionic site (PAS) of Electrophorus electricus AChE (EeAChE) and competitively displace propidium iodide from this site. Moreover, we examined the ability of MB-gCs to scavenge free radicals as well as their influence on mitochondrial potential and iron-induced lipid peroxidation. We found that MB-gCs effectively inhibited AChE and BChE with IC 50 values in the range 1.73–10.5 μM and exhibited low potencies against CaE (9.8–26[%] inhibition at 20 μM). Kinetic studies showed that MB-gCs were mixed-type reversible inhibitors of both cholinesterases. Molecular docking results showed that the MB-gCs could bind both to the catalytic active site and to the P