Details

Autor(en) / Beteiligte

• ElNaggar, Mai H.
• Elgazar, Abdullah A.
• Gamal, Ghada
• Hamed, Shimaa M.
• Elsayed, Zainab M.
• El-Ashrey, Mohamed K.
• Abood, Amira
• El Hassab, Mahmoud A.
• Soliman, Ahmed M.
• El-Domany, Ramadan A.
• Badria, Farid A.
• Supuran, Claudiu T.
• Eldehna, Wagdy M.

Titel

Identification of sulphonamide-tethered N-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease

Ist Teil von

• Journal of enzyme inhibition and medicinal chemistry, 2023-12, Vol.38 (1), p.2234665-2234665

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• 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 6b showed promising inhibitory activity with an IC 50 = 0.249 µM. Additionally, 6b inhibited viral cell proliferation with an IC 50 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. In silico analysis of 6b disclosed its ability to interact with key residues in the enzyme active site, supporting the obtained in vitro findings.