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

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...

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Autores principales: Wu, Jing, Feng, Bo, Gao, Li-Xin, Zhang, Chun, Li, Jia, Xiang, Da-Jun, Zang, Yi, Wang, Wen-Long
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145245/
https://www.ncbi.nlm.nih.gov/pubmed/35630836
http://dx.doi.org/10.3390/molecules27103359
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author Wu, Jing
Feng, Bo
Gao, Li-Xin
Zhang, Chun
Li, Jia
Xiang, Da-Jun
Zang, Yi
Wang, Wen-Long
author_facet Wu, Jing
Feng, Bo
Gao, Li-Xin
Zhang, Chun
Li, Jia
Xiang, Da-Jun
Zang, Yi
Wang, Wen-Long
author_sort Wu, Jing
collection PubMed
description 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 IC(50) 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).
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spelling pubmed-91452452022-05-29 Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors Wu, Jing Feng, Bo Gao, Li-Xin Zhang, Chun Li, Jia Xiang, Da-Jun Zang, Yi Wang, Wen-Long Molecules Article 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 IC(50) 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). MDPI 2022-05-23 /pmc/articles/PMC9145245/ /pubmed/35630836 http://dx.doi.org/10.3390/molecules27103359 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Jing
Feng, Bo
Gao, Li-Xin
Zhang, Chun
Li, Jia
Xiang, Da-Jun
Zang, Yi
Wang, Wen-Long
Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title_full Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title_fullStr Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title_full_unstemmed Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title_short Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
title_sort synthesis and biochemical evaluation of 8h-indeno[1,2-d]thiazole derivatives as novel sars-cov-2 3cl protease inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9145245/
https://www.ncbi.nlm.nih.gov/pubmed/35630836
http://dx.doi.org/10.3390/molecules27103359
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