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

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...

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Autores principales: Dalinger, A. I., Baev, D. S., Yarovaya, O. I., Chirkova, V. Yu., Sharlaeva, E. A., Belenkaya, S. V., Shcherbakov, D. N., Salakhutdinov, N. F., Vatsadze, S. Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
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Full Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926410/
https://www.ncbi.nlm.nih.gov/pubmed/36817558
http://dx.doi.org/10.1007/s11172-023-3729-x
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author Dalinger, A. I.
Baev, D. S.
Yarovaya, O. I.
Chirkova, V. Yu.
Sharlaeva, E. A.
Belenkaya, S. V.
Shcherbakov, D. N.
Salakhutdinov, N. F.
Vatsadze, S. Z.
author_facet Dalinger, A. I.
Baev, D. S.
Yarovaya, O. I.
Chirkova, V. Yu.
Sharlaeva, E. A.
Belenkaya, S. V.
Shcherbakov, D. N.
Salakhutdinov, N. F.
Vatsadze, S. Z.
author_sort Dalinger, A. I.
collection PubMed
description 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 (IC(50) = 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 (IC(50) = 100±5.7µmol L(−1)) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.
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spelling pubmed-99264102023-02-14 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. Chirkova, V. Yu. Sharlaeva, E. A. Belenkaya, S. V. Shcherbakov, D. N. Salakhutdinov, N. F. Vatsadze, S. Z. Russ Chem Bull Full Articles 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 (IC(50) = 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 (IC(50) = 100±5.7µmol L(−1)) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data. Springer US 2023-02-14 2023 /pmc/articles/PMC9926410/ /pubmed/36817558 http://dx.doi.org/10.1007/s11172-023-3729-x Text en © Springer Science+Business Media LLC 2023 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Full Articles
Dalinger, A. I.
Baev, D. S.
Yarovaya, O. I.
Chirkova, V. Yu.
Sharlaeva, E. A.
Belenkaya, S. V.
Shcherbakov, D. N.
Salakhutdinov, N. F.
Vatsadze, S. Z.
Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title_full Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title_fullStr Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title_full_unstemmed Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title_short Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
title_sort synthesis of non-symmetric n-benzylbispidinol amides and study of their inhibitory activity against the main protease of the sars-cov-2 virus
topic Full Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926410/
https://www.ncbi.nlm.nih.gov/pubmed/36817558
http://dx.doi.org/10.1007/s11172-023-3729-x
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