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 (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 an...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2022-05, Vol.27 (10), p.3359
Main Authors: Wu, Jing, Feng, Bo, Gao, Li-Xin, Zhang, Chun, Li, Jia, Xiang, Da-Jun, Zang, Yi, Wang, Wen-Long
Format: Article
Language:English
Subjects:
Binding sites
Chymotrypsin
Coronaviruses
COVID-19
Cysteine proteinase
drug design and synthesis
Molecular docking
Mpro inhibitors
Protease
Protease inhibitors
Proteinase inhibitors
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
structure-activity relationships (SAR)
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cited_by cdi_FETCH-LOGICAL-c470t-fb72757004e0955a7f71418be5098429e6a38b6178396c82c02d66941458a8cf3
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container_title Molecules (Basel, Switzerland)
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creator Wu, Jing
Feng, Bo
Gao, Li-Xin
Zhang, Chun
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Xiang, Da-Jun
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Wang, Wen-Long
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 (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 IC50 of 1.28 ± 0.17 μM against SARS-CoV-2 3CLpro. Molecular docking of 7a against 3CLpro 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 3CLpro.
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subjects Binding sites
Chymotrypsin
Coronaviruses
COVID-19
Cysteine proteinase
drug design and synthesis
Molecular docking
Mpro inhibitors
Protease
Protease inhibitors
Proteinase inhibitors
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
structure-activity relationships (SAR)
title Synthesis and Biochemical Evaluation of 8H-Indeno[1,2-d]thiazole Derivatives as Novel SARS-CoV-2 3CL Protease Inhibitors
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