Identification of Sulphonamide-tethered -((triazol-4-yl)methyl)isatin Derivatives As Inhibitors of SARS-CoV-2 Main Protease

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2023 Jul 12

PMID 37434404

Authors

Mai H ElNaggar

Abdullah A Elgazar

Ghada Gamal

Shimaa M Hamed

Zainab M Elsayed

Mohamed K El-Ashrey

Amira Abood

Mahmoud A El Hassab

Ahmed M Soliman

Ramadan A El-Domany

Farid A Badria

Claudiu T Supuran

Wagdy M Eldehna

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel triazolo-isatins for inhibiting main protease (Mpro) of the virus, a crucial enzyme for its replication in the host cells. Particularly, sulphonamide showed promising inhibitory activity with an IC= 0.249 µM. Additionally, inhibited viral cell proliferation with an IC of 4.33 µg/ml, and was non-toxic to VERO-E6 cells (CC50 = 564.74 µg/ml) displaying a selectivity index of 130.4. analysis of disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained findings.

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