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d-Alanyl:d-alanine ligase inhibitors as antibacterial agents against Staphylococcus aureus: a review

Mohammed Afzal Azam1, Abisha Thomas2, Srikanth Jupudi2

  • 1College of Pharmacy, JSS University, Noida, Uttar Pradesh, India.

Nucleosides, Nucleotides & Nucleic Acids
|April 27, 2026
PubMed

Insights

Developing new antibacterial agents is crucial due to rising antibiotic resistance. Inhibiting D-alanyl:D-alanine ligase, essential for bacterial cell walls, offers a promising strategy against Staphylococcus aureus infections.

Area of Science:

  • Microbiology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Staphylococcus aureus is a major global pathogen causing significant mortality and morbidity.
  • The rise of multidrug-resistant strains necessitates novel antibacterial therapies.
  • ATP-dependent D-alanyl:D-alanine ligase is a validated target for antibacterial drug development due to its essential role in peptidoglycan synthesis.

Purpose of the Study:

  • To explore the potential of inhibiting D-alanyl:D-alanine ligase as a strategy against Staphylococcus aureus.
  • To review existing inhibitors of D-alanyl:D-alanine ligase and their antibacterial activities.

Main Methods:

  • Literature review of studies investigating D-alanyl:D-alanine ligase inhibitors.
  • Analysis of reported antibacterial activities of various inhibitor classes against Staphylococcus aureus.

Main Results:

  • Several classes of D-alanyl:D-alanine ligase inhibitors, including N-acyl-substituted sulfamides, thiosemicarbazides, benzoxazoles, and diazenedicarboxamides, have demonstrated significant activity.
  • These inhibitors show potential in combating Staphylococcus aureus infections.

Conclusions:

  • Inhibition of D-alanyl:D-alanine ligase is a viable and effective strategy for discovering new antibacterial agents.
  • Further development of D-alanyl:D-alanine ligase inhibitors could lead to novel treatments for Staphylococcus aureus infections, addressing the challenge of antibiotic resistance.
Keywords:
Ddl inhibitorsIC50MICStaphylococcus aureusantibacterial activity

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