New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS-CoV-2

ChemMedChem. 2021 Nov 19;16(22):3418-3427. doi: 10.1002/cmdc.202100476. Epub 2021 Sep 6.

Abstract

Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates (5 d-g) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).

Keywords: 1,2,3-Triazole; Benzothiazole; Computational studies; Pyrazine; SARS-CoV-2.

MeSH terms

  • Amides / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • Chlorocebus aethiops
  • Coronavirus RNA-Dependent RNA Polymerase / metabolism
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Pyrazines / chemical synthesis
  • Pyrazines / metabolism
  • Pyrazines / pharmacology*
  • Pyrazines / toxicity
  • Quantitative Structure-Activity Relationship
  • SARS-CoV-2 / drug effects*
  • Vero Cells

Substances

  • Amides
  • Antiviral Agents
  • Pyrazines
  • Coronavirus RNA-Dependent RNA Polymerase
  • NSP12 protein, SARS-CoV-2
  • favipiravir