ACS Medicinal Chemistry Letters, volume 13, issue 1, pages 140-147

Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors

Shcherbakov Dmitriy N. 1, 2
Dalinger Alexander 4
Belenkaya Svetlana 1, 6
Khvostov Aleksei 4
Krutko D P 4
Volosnikova Ekaterina 1
Sharlaeva Elena 2
Shanshin Daniil 1
Tolstikova Tatyana 3
Kolosova Irina V 1
Publication typeJournal Article
Publication date2021-09-29
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor4.2
ISSN19485875
Organic Chemistry
Drug Discovery
Biochemistry
Abstract
For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active site of the protease, a group of compounds were modeled and tested for activity against 3CLpro. The 3CLpro activity was measured using the fluorogenic substrate Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by comparison with literature data for ebselen and disulfiram. The results of the experiments performed with bispidine compounds showed that 14 compounds exhibited activity in the concentration range 1–10 μM, and 3 samples exhibited submicromolar activity. The structure–activity relationship studies showed that the molecules containing a carbonyl group in the ninth position of the bicycle exhibited the maximum activity. Based on the experimental and theoretical results obtained, further directions for the development of this topic were proposed.

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Shcherbakov D. N. et al. Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors // ACS Medicinal Chemistry Letters. 2021. Vol. 13. No. 1. pp. 140-147.
GOST all authors (up to 50) Copy
Shcherbakov D. N., S. Baev D., Kalinin M. A., Dalinger A., Chirkova V., Belenkaya S., Khvostov A., Krutko D. P., Medvedko A. V., Volosnikova E., Sharlaeva E., Shanshin D., Tolstikova T., Yarovaya O. I., Kolosova I. V., Salakhutdinov N. F., Vatsadze S. Z. Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors // ACS Medicinal Chemistry Letters. 2021. Vol. 13. No. 1. pp. 140-147.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1021/acsmedchemlett.1c00299
UR - https://doi.org/10.1021%2Facsmedchemlett.1c00299
TI - Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors
T2 - ACS Medicinal Chemistry Letters
AU - Chirkova, Varvara
AU - Belenkaya, Svetlana
AU - Khvostov, Aleksei
AU - Volosnikova, Ekaterina
AU - Sharlaeva, Elena
AU - Shanshin, Daniil
AU - Dalinger, Alexander
AU - Tolstikova, Tatyana
AU - Medvedko, Alexey V
AU - Yarovaya, Olga I.
AU - Vatsadze, Sergey Z.
AU - Shcherbakov, Dmitriy N.
AU - S. Baev, Dmitry
AU - Kalinin, Mikhail A
AU - Krutko, D P
AU - Kolosova, Irina V
AU - Salakhutdinov, Nariman F.
PY - 2021
DA - 2021/09/29 00:00:00
PB - American Chemical Society (ACS)
SP - 140-147
IS - 1
VL - 13
SN - 1948-5875
ER -
BibTex |
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BibTex Copy
@article{2021_Shcherbakov
author = {Varvara Chirkova and Svetlana Belenkaya and Aleksei Khvostov and Ekaterina Volosnikova and Elena Sharlaeva and Daniil Shanshin and Alexander Dalinger and Tatyana Tolstikova and Alexey V Medvedko and Olga I. Yarovaya and Sergey Z. Vatsadze and Dmitriy N. Shcherbakov and Dmitry S. Baev and Mikhail A Kalinin and D P Krutko and Irina V Kolosova and Nariman F. Salakhutdinov},
title = {Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors},
journal = {ACS Medicinal Chemistry Letters},
year = {2021},
volume = {13},
publisher = {American Chemical Society (ACS)},
month = {sep},
url = {https://doi.org/10.1021%2Facsmedchemlett.1c00299},
number = {1},
pages = {140--147},
doi = {10.1021/acsmedchemlett.1c00299}
}
MLA
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Shcherbakov, Dmitriy N., et al. “Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors.” ACS Medicinal Chemistry Letters, vol. 13, no. 1, Sep. 2021, pp. 140-147. https://doi.org/10.1021%2Facsmedchemlett.1c00299.
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