Synthesis, molecular docking studies, and in vitro antimicrobial evaluation of piperazine and triazolo-pyrazine derivatives

Mol Divers. 2022 Apr;26(2):827-841. doi: 10.1007/s11030-021-10190-x. Epub 2021 Feb 5.

Abstract

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by 1H NMR, 13C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography. In vitro screening of the antimicrobial activity of all compounds (3a-t) was evaluated against five bacterial and two fungal strains. This study disclosed that N-{[(3-chlorophenyl)]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)}piperazine-1-carboxamide (3o) was the superior antimicrobial with good growth inhibition against A. baumannii. Furthermore, the results from the performed molecular docking studies were promising, since the observed data could be used to develop more potent antimicrobials.

Keywords: Antimicrobial activity; Molecular docking; Piperazine derivatives; Synthesis; Triazolo-pyrazine.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / chemistry
  • Anti-Infective Agents* / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Piperazine
  • Pyrazines* / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Pyrazines
  • Piperazine