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

Molecules. 2022 May 23;27(10):3359. doi: 10.3390/molecules27103359.

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 (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.

Keywords: COVID-19; Mpro inhibitors; drug design and synthesis; structure-activity relationships (SAR).

MeSH terms

  • COVID-19 Drug Treatment*
  • Cysteine Endopeptidases / chemistry
  • Humans
  • Molecular Docking Simulation
  • Pandemics
  • Protease Inhibitors* / chemistry
  • Protease Inhibitors* / pharmacology
  • SARS-CoV-2
  • Thiazoles / pharmacology
  • Viral Proteins / metabolism

Substances

  • Protease Inhibitors
  • Thiazoles
  • Viral Proteins
  • Cysteine Endopeptidases