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2023-08-17

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cc-by-nc-nd (c) Jiang, Xiangyi et al., 2023
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/229208

Identification of novel 123-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors <em>via</em> click-chemistry-based rapid screening

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https://doi.org/10.1039/d3md00306j

Resum

SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The N-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CLpro inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using clickchemistry-based miniaturized synthesis and their 3CLpro inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds D1N8 (IC50 =0.44± 0.12 μM) and D1N52 (IC50 = 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CLpro, being equivalent to that of L-26 (IC50 =0.30± 0.14 μM). In addition, the cytotoxicity of D1N8 (CC50 >20 μM) and D1N52 (CC50 >20 μM) decreased significantly compared with L-26 (CC50 <2.6 μM). Further molecular dynamics simulations revealed the potential binding interactions between D1N52 and SARS-CoV-2 3CLpro. These efforts lay a solid foundation for the research of novel anti-SARS-CoV-2 agents targeting 3CLpro.

Matèries

SARS-CoV-2, COVID-19

Matèries (anglès)

SARS-CoV-2, COVID-19

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Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

Citació

TOLLEFSON, Ann E., et al. Identification of novel 123-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors via click-chemistry-based rapid screening. RSC Medicinal Chemistry. 2023. Vol. 14, num. 10, pags. 2068-2078. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/229208

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