Development of Single-Stranded DNA Bisintercalating Inhibitors of Primase DnaG as Antibiotics

Keith D. Green, Ankita Punetha, Nishad Thamban Chandrika, Caixia Hou, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Many essential enzymes in bacteria remain promising potential targets of antibacterial agents. In this study, we discovered that dequalinium, a topical antibacterial agent, is an inhibitor of Staphylococcus aureus primase DnaG (SaDnaG) with low-micromolar minimum inhibitory concentrations against several S. aureus strains, including methicillin-resistant bacteria. Mechanistic studies of dequalinium and a series of nine of its synthesized analogues revealed that these compounds are single-stranded DNA bisintercalators that penetrate a bacterium by compromising its membrane. The best compound of this series likely interacts with DnaG directly, inhibits both staphylococcal cell growth and biofilm formation, and displays no significant hemolytic activity or toxicity to mammalian cells. This compound is an excellent lead for further development of a novel anti-staphylococcal therapeutic.

Original languageEnglish
Pages (from-to)1986-1995
Number of pages10
Issue number12
StatePublished - Jun 17 2021

Bibliographical note

Publisher Copyright:
© 2021 Wiley-VCH GmbH


  • DNA intercalators
  • Staphylococcus aureus
  • antibacterial agents
  • library screening
  • medicinal chemistry

ASJC Scopus subject areas

  • Drug Discovery
  • General Pharmacology, Toxicology and Pharmaceutics
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry


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