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Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors. / Shcherbakov, Dmitriy; Baev, Dmitriy; Kalinin, Mikhail et al.

In: ACS Medicinal Chemistry Letters, Vol. 13, No. 1, 13.01.2022, p. 140-147.

Research output: Contribution to journal › Article › peer-review

Harvard

Shcherbakov, D, Baev, D, Kalinin, M, Dalinger, A, Chirkova, V, Belenkaya, S, Khvostov, A, Krut'Ko, D, Medved'Ko, A, Volosnikova, E, Sharlaeva, E, Shanshin, D, Tolstikova, T, Yarovaya, O, Maksyutov, R, Salakhutdinov, N & Vatsadze, S 2022, 'Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors', ACS Medicinal Chemistry Letters, vol. 13, no. 1, pp. 140-147. https://doi.org/10.1021/acsmedchemlett.1c00299

APA

Shcherbakov, D., Baev, D., Kalinin, M., Dalinger, A., Chirkova, V., Belenkaya, S., Khvostov, A., Krut'Ko, D., Medved'Ko, A., Volosnikova, E., Sharlaeva, E., Shanshin, D., Tolstikova, T., Yarovaya, O., Maksyutov, R., Salakhutdinov, N., & Vatsadze, S. (2022). Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors. ACS Medicinal Chemistry Letters, 13(1), 140-147. https://doi.org/10.1021/acsmedchemlett.1c00299

Vancouver

Shcherbakov D, Baev D, Kalinin M, Dalinger A, Chirkova V, Belenkaya S et al. Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors. ACS Medicinal Chemistry Letters. 2022 Jan 13;13(1):140-147. Epub 2021 Sept 29. doi: 10.1021/acsmedchemlett.1c00299

Author

Shcherbakov, Dmitriy ; Baev, Dmitriy ; Kalinin, Mikhail et al. / Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors. In: ACS Medicinal Chemistry Letters. 2022 ; Vol. 13, No. 1. pp. 140-147.

BibTeX

@article{262595c42ee04c6e9bf85871e5515782,
title = "Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors",
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. ",
keywords = "3,7-diazabicyclo[3.3.1]nonane, bispidinone, inhibition, molecular docking, SARS-CoV-2 main viral protease",
author = "Dmitriy Shcherbakov and Dmitriy Baev and Mikhail Kalinin and Alexander Dalinger and Varvara Chirkova and Svetlana Belenkaya and Aleksei Khvostov and Dmitry Krut'Ko and Aleksei Medved'Ko and Ekaterina Volosnikova and Elena Sharlaeva and Daniil Shanshin and Tatyana Tolstikova and Olga Yarovaya and Rinat Maksyutov and Nariman Salakhutdinov and Sergey Vatsadze",
note = "Funding Information: The reported study was funded by RFBR according to the Research Project No. 20-04-60215. The authors express sincere gratitude to Kudriashova Elena for help in creating graphical abstract. Publisher Copyright: {\textcopyright} ",
year = "2022",
month = jan,
day = "13",
doi = "10.1021/acsmedchemlett.1c00299",
language = "English",
volume = "13",
pages = "140--147",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "1",

}

RIS

TY - JOUR

T1 - Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors

AU - Shcherbakov, Dmitriy

AU - Baev, Dmitriy

AU - Kalinin, Mikhail

AU - Dalinger, Alexander

AU - Chirkova, Varvara

AU - Belenkaya, Svetlana

AU - Khvostov, Aleksei

AU - Krut'Ko, Dmitry

AU - Medved'Ko, Aleksei

AU - Volosnikova, Ekaterina

AU - Sharlaeva, Elena

AU - Shanshin, Daniil

AU - Tolstikova, Tatyana

AU - Yarovaya, Olga

AU - Maksyutov, Rinat

AU - Salakhutdinov, Nariman

AU - Vatsadze, Sergey

N1 - Funding Information: The reported study was funded by RFBR according to the Research Project No. 20-04-60215. The authors express sincere gratitude to Kudriashova Elena for help in creating graphical abstract. Publisher Copyright: ©

PY - 2022/1/13

Y1 - 2022/1/13

N2 - 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.

AB - 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.

KW - 3,7-diazabicyclo[3.3.1]nonane

KW - bispidinone

KW - inhibition

KW - molecular docking

KW - SARS-CoV-2 main viral protease

UR - http://www.scopus.com/inward/record.url?scp=85117233350&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/ce42ba87-ae7e-3879-becc-6c7e5529637b/

U2 - 10.1021/acsmedchemlett.1c00299

DO - 10.1021/acsmedchemlett.1c00299

M3 - Article

C2 - 35043075

AN - SCOPUS:85117233350

VL - 13

SP - 140

EP - 147

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

SN - 1948-5875

IS - 1

ER -

ID: 34447322