Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus

A I Dalinger; D S Baev; O I Yarovaya; V Yu Chirkova; E A Sharlaeva; S V Belenkaya; D N Shcherbakov; N F Salakhutdinov; S Z Vatsadze

doi:10.1007/s11172-023-3729-x

Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus

Переведенное название: Синтез несимметричных амидов N-бензилбиспидинола и изучение их ингибирующей активности по отношению к основной вирусной протеазе SARS-CoV-2

A I Dalinger, D S Baev, O I Yarovaya, V Yu Chirkova, E A Sharlaeva, S V Belenkaya, D N Shcherbakov, N F Salakhutdinov, S Z Vatsadze

Результат исследования: Научные публикации в периодических изданиях › статья › рецензирование

Аннотация

На основании данных, полученных с помощью молекулярного моделирования нековалентного взаимодействия несимметричных амидов N-бензилбиспидин-9-ола с активным сайтом основной протеазы SARS-CoV-2 (3CLpro), синтезирован ряд соединений и исследована их ингибирующая активность по отношению к 3СLpro в сравнении с известным ингибитором ML188 (IC50 = 1.56±0.55 мкмоль•л-1). Установлено, что только соединение 1g, содержащее 1,4-дигидроиндено[1,2-c]пиразольный фрагмент, проявляет умеренную активность (IC50 = 100±5.7 мкмоль•л-1) и обладает наиболее высоким расчетным значением энергии связывания среди изученных производных биспидина, согласно данным молекулярного докинга.

Переведенное название	Синтез несимметричных амидов N-бензилбиспидинола и изучение их ингибирующей активности по отношению к основной вирусной протеазе SARS-CoV-2
Язык оригинала	английский
Страницы (с-по)	239-247
Число страниц	9
Журнал	Russian Chemical Bulletin
Том	72
Номер выпуска	1
DOI	https://doi.org/10.1007/s11172-023-3729-x
Состояние	Опубликовано - 1 янв. 2023

Предметные области OECD FOS+WOS

1.04 ХИМИЧЕСКИЕ НАУКИ

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10.1007/s11172-023-3729-x

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https://www.mendeley.com/catalogue/90187cc5-c76c-314a-8fe4-5ada7f3cef5b/

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Dalinger, A. I., Baev, D. S., Yarovaya, O. I., Chirkova, V. Y., Sharlaeva, E. A., Belenkaya, S. V., Shcherbakov, D. N., Salakhutdinov, N. F., & Vatsadze, S. Z. (2023). Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus. Russian Chemical Bulletin, 72(1), 239-247. https://doi.org/10.1007/s11172-023-3729-x

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title = "Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus",

abstract = "Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC50 = 1.56±0.55 µmol L-1). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity (IC50 = 100±5.7µmol L-1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.",

keywords = "3CLpro, SARS-CoV-2, amides, bispidine, inhibition, main viral protease, molecular docking",

author = "Dalinger, {A I} and Baev, {D S} and Yarovaya, {O I} and Chirkova, {V Yu} and Sharlaeva, {E A} and Belenkaya, {S V} and Shcherbakov, {D N} and Salakhutdinov, {N F} and Vatsadze, {S Z}",

note = "This work was performed under fi nancial support of the Russian Foundation for Basic Research (Project No. 20-04-60215). Biological testing was carried out under fi nancial support of Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2021-1355 dated 12.10.2021) as part of the implementation of certain activities of the Federal Scientifi c and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019—2027. {\textcopyright} Springer Science+Business Media LLC 2023.",

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doi = "10.1007/s11172-023-3729-x",

language = "English",

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Dalinger, AI, Baev, DS, Yarovaya, OI, Chirkova, VY, Sharlaeva, EA, Belenkaya, SV , Shcherbakov, DN , Salakhutdinov, NF & Vatsadze, SZ 2023, 'Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus', Russian Chemical Bulletin, том. 72, № 1, стр. 239-247. https://doi.org/10.1007/s11172-023-3729-x

Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus. / Dalinger, A I; Baev, D S; Yarovaya, O I и др.

В: Russian Chemical Bulletin, Том 72, № 1, 01.01.2023, стр. 239-247.

Результат исследования: Научные публикации в периодических изданиях › статья › рецензирование

TY - JOUR

T1 - Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus

AU - Dalinger, A I

AU - Baev, D S

AU - Yarovaya, O I

AU - Chirkova, V Yu

AU - Sharlaeva, E A

AU - Belenkaya, S V

AU - Shcherbakov, D N

AU - Salakhutdinov, N F

AU - Vatsadze, S Z

N1 - This work was performed under fi nancial support of the Russian Foundation for Basic Research (Project No. 20-04-60215). Biological testing was carried out under fi nancial support of Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2021-1355 dated 12.10.2021) as part of the implementation of certain activities of the Federal Scientifi c and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019—2027. © Springer Science+Business Media LLC 2023.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC50 = 1.56±0.55 µmol L-1). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity (IC50 = 100±5.7µmol L-1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.

AB - Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC50 = 1.56±0.55 µmol L-1). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity (IC50 = 100±5.7µmol L-1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.

KW - 3CLpro

KW - SARS-CoV-2

KW - amides

KW - bispidine

KW - inhibition

KW - main viral protease

KW - molecular docking

UR - https://www.mendeley.com/catalogue/90187cc5-c76c-314a-8fe4-5ada7f3cef5b/

U2 - 10.1007/s11172-023-3729-x

DO - 10.1007/s11172-023-3729-x

M3 - Article

C2 - 36817558

VL - 72

SP - 239

EP - 247

JO - Russian Chemical Bulletin

JF - Russian Chemical Bulletin

SN - 1066-5285

IS - 1

ER -