Design, Synthesis, Molecular Docking, and ADME-Tox Investigations of Imidazo[1,2-a]Pyrimidines Derivatives as Antimicrobial Agents

Molecules. 2024 Oct 26;29(21):5058. doi: 10.3390/molecules29215058.

Abstract

A convenient and effective synthesis of imidazo[1,2-a]pyrimidine derivatives has been developed under microwave irradiations using Al2O3 as a catalyst in solvent-free conditions. The functionalized imidazo[1,2-a]pyrimidine derivatives are useful in biochemistry and medical science. In our investigation, the antimicrobial activity of the synthesized compounds was evaluated against 13 microorganisms, including 6 Gram-positive bacteria, 4 Gram-negative bacteria, and 3 pathogenic fungi. Bioactivity tests revealed that the majority of the compounds exhibited good antimicrobial activity. Finally, molecular docking simulations and ADME-T predictions were performed, showing that the most active compounds have good binding modes with microbial targets and promising pharmacokinetic safety profiles.

Keywords: Al2O3 catalyst; antimicrobial activity; imidazo[1,2-a]pyrimidine; in silico study; microwave; solvent free.

MeSH terms

  • Anti-Infective Agents* / chemical synthesis
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Drug Design*
  • Fungi / drug effects
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Microbial Sensitivity Tests*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology
  • Structure-Activity Relationship

Substances

  • Pyrimidines
  • Anti-Infective Agents
  • Imidazoles

Grants and funding

The authors are grateful to the Directorate General for Scientific Research and Technological Development (DGRSDT) and the University of Tlemcen for their financial support. JAS and MPVT thank the Ministerio de Ciencia y Tecnología (Project MAT2017-86109P) for financial support.