Development of potent and effective SARS-CoV-2 main protease inhibitors based on maleimide analogs for the potential treatment of COVID-19

Karol Biernacki; Olga Ciupak; Mateusz Daśko; Janusz Rachoń; Damian Flis; Justyna Budka; Iwona Inkielewicz-Stępniak; Anna Czaja; Janusz Rak; Sebastian Demkowicz

doi:10.1080/14756366.2023.2290910

Development of potent and effective SARS-CoV-2 main protease inhibitors based on maleimide analogs for the potential treatment of COVID-19

Abstract

In the present work, we report a new series of potent SARS-CoV-2 Main Protease (Mpro) inhibitors based on maleimide derivatives. The inhibitory activities were tested in an enzymatic assay using recombinant Mpro (3CL Protease from coronavirus SARS-CoV-2). Within the set of new Mpro inhibitors, 6e demonstrated the highest activity in the enzymatic assay with an IC50 value of 8.52 ± 0.44 mM. The IC50 value for Nirmatrelvir (PF-07321332, used as a reference) was 0.84 ± 0.37 mM. The cytotoxic properties were determined in the MTT assay using MRC-5 and HEK-293 cell lines. In the course of the investigation, we found that the newly obtained maleimide derivatives are not substantially cytotoxic (IC50 values for most compounds were above 200 mM).

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Authors (10)

Karol Biernacki dr inż.
Olga Ciupak mgr inż.
Mateusz Daśko dr inż.
Janusz Rachoń prof. dr hab. inż.
Damian Flis dr
- Katedra i Zakład Patofizjologii Farmaceutycznej Wydział Farmaceutyczn
Justyna Budka mgr
Iwona Inkielewicz-Stępniak
Anna Czaja
Janusz Rak Prof.
Sebastian Demkowicz dr hab. inż.

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Articles

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artykuły w czasopismach

Published in:

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY no. 39,
ISSN: 1475-6366

Language:

Polish

Publication year:

2024

Bibliographic description:

Biernacki K., Ciupak O., Daśko M., Rachoń J., Flis D., Budka J., Inkielewicz-Stępniak I., Czaja A., Rak J., Demkowicz S.: Development of potent and effective SARS-CoV-2 main protease inhibitors based on maleimide analogs for the potential treatment of COVID-19// JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY -Vol. 39,iss. 1 (2024), s.229091-

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