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

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 May 28

PMID 35630836

Authors

Jing Wu

Bo Feng

Li-Xin Gao

Chun Zhang

Jia Li

Da-Jun Xiang

Yi Zang

Wen-Long Wang

Affiliations

Soon will be listed here.

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) becomes an attractive target for SARS-CoV-2 due to its important role in viral replication. We synthesized a series of 8-indeno[1,2-]thiazole derivatives and evaluated their biochemical activities against SARS-CoV-2 3CL. Among them, the representative compound displayed inhibitory activity with an IC of 1.28 ± 0.17 μM against SARS-CoV-2 3CL. Molecular docking of against 3CL 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.

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References

Wang C, Horby P, Hayden F, Gao G . A novel coronavirus outbreak of global health concern. Lancet. 2020; 395(10223):470-473. PMC: 7135038. DOI: 10.1016/S0140-6736(20)30185-9. View

. COVID-19 Vaccine Breakthrough Infections Reported to CDC - United States, January 1-April 30, 2021. MMWR Morb Mortal Wkly Rep. 2021; 70(21):792-793. PMC: 8158893. DOI: 10.15585/mmwr.mm7021e3. View

Wen W, Chen C, Tang J, Wang C, Zhou M, Cheng Y . Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19：a meta-analysis. Ann Med. 2022; 54(1):516-523. PMC: 8820829. DOI: 10.1080/07853890.2022.2034936. View

Wu Q, Yan S, Wang Y, Li M, Xiao Y, Li Y . Discovery of 4'-O-methylscutellarein as a potent SARS-CoV-2 main protease inhibitor. Biochem Biophys Res Commun. 2022; 604:76-82. PMC: 8907111. DOI: 10.1016/j.bbrc.2022.03.052. View

. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020; 5(4):536-544. PMC: 7095448. DOI: 10.1038/s41564-020-0695-z. View

Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y . Structure of M from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020; 582(7811):289-293. DOI: 10.1038/s41586-020-2223-y. View

Mody V, Ho J, Wills S, Mawri A, Lawson L, Ebert M . Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. Commun Biol. 2021; 4(1):93. PMC: 7817688. DOI: 10.1038/s42003-020-01577-x. View

Macchiagodena M, Pagliai M, Procacci P . Characterization of the non-covalent interaction between the PF-07321332 inhibitor and the SARS-CoV-2 main protease. J Mol Graph Model. 2021; 110:108042. PMC: 8491126. DOI: 10.1016/j.jmgm.2021.108042. View

Dai W, Zhang B, Jiang X, Su H, Li J, Zhao Y . Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020; 368(6497):1331-1335. PMC: 7179937. DOI: 10.1126/science.abb4489. View

10.

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

11.

Han S, Goins C, Arya T, Shin W, Maw J, Hooper A . Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CL). J Med Chem. 2021; 65(4):2880-2904. PMC: 8353992. DOI: 10.1021/acs.jmedchem.1c00598. View

12.

Catlin N, Bowman C, Campion S, Cheung J, Nowland W, Sathish J . Reproductive and developmental safety of nirmatrelvir (PF-07321332), an oral SARS-CoV-2 M inhibitor in animal models. Reprod Toxicol. 2022; 108:56-61. PMC: 8801796. DOI: 10.1016/j.reprotox.2022.01.006. View

13.

Zhao Y, Fang C, Zhang Q, Zhang R, Zhao X, Duan Y . Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332. Protein Cell. 2021; 13(9):689-693. PMC: 8533666. DOI: 10.1007/s13238-021-00883-2. View

14.

Chen J, Wang R, Gilby N, Wei G . Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance. J Chem Inf Model. 2022; 62(2):412-422. PMC: 8751645. DOI: 10.1021/acs.jcim.1c01451. View

15.

Xiong M, Nie T, Shao Q, Li M, Su H, Xu Y . In silico screening-based discovery of novel covalent inhibitors of the SARS-CoV-2 3CL protease. Eur J Med Chem. 2022; 231:114130. PMC: 8783839. DOI: 10.1016/j.ejmech.2022.114130. View

16.

Kocyigit U, Aslan O, Gulcin I, Temel Y, Ceylan M . Synthesis and Carbonic Anhydrase Inhibition of Novel 2-(4-(Aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione Derivatives. Arch Pharm (Weinheim). 2016; 349(12):955-963. DOI: 10.1002/ardp.201600092. View

17.

Meng X, Gao L, Wang Z, Feng B, Zhang C, Satheeshkumar R . Synthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Bioorg Chem. 2021; 116:105384. DOI: 10.1016/j.bioorg.2021.105384. View

18.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

19.

Vkovski P, Kratzel A, Steiner S, Stalder H, Thiel V . Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2020; 19(3):155-170. PMC: 7592455. DOI: 10.1038/s41579-020-00468-6. View

20.

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View