Antibacterial activity and mechanism of action of the benzazole acrylonitrile-based compounds: In vitro, spectroscopic, and docking studies

Shaikha S. AlNeyadi, Alaa A. Salem, Mohammad A. Ghattas, Noor Atatreh, Ibrahim M. Abdou

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with = 1.0 μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC = 1.0–1.5 μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.

Original languageEnglish
Pages (from-to)270-282
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Volume136
DOIs
Publication statusPublished - 2017

Keywords

  • Antibacterial
  • Docking
  • PBP
  • Pyrimidine
  • Synthesis
  • β-lactamase

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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