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Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors.

ABSTRACT: The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CL^pro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CL^pro. Among them, the representative compound 7a displayed inhibitory activity with an IC₅₀ of 1.28 ± 0.17 μM against SARS-CoV-2 3CL^pro. Molecular docking of 7a against 3CL^pro was performed and the binding mode was rationalized. These preliminary results provide a unique prototype for the development of novel inhibitors against SARS-CoV-2 3CL^pro.

SUBMITTER: Wu J

PROVIDER: S-EPMC9145245 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors.

Wu Jing J Feng Bo B Gao Li-Xin LX Zhang Chun C Li Jia J Xiang Da-Jun DJ Zang Yi Y Wang Wen-Long WL

Molecules (Basel, Switzerland) 20220523 10

The COVID-19 pandemic caused by SARS-CoV-2 is a global burden on human health and economy. The 3-Chymotrypsin-like cysteine protease (3CLpro) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8H-indeno[1,2-d]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CLpro. Among them, the representative compound 7a displayed inhibitory activity with an IC5 ...[more]

PMID: 35630836

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