In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria

Antimicrob Agents Chemother. 2000 Aug;44(8):2217-21. doi: 10.1128/AAC.44.8.2217-2221.2000.


The 6-anilinouracils are novel dGTP analogs that selectively inhibit the replication-specific DNA polymerase III of gram-positive eubacteria. Two specific derivatives, IMAU (6-[3'-iodo-4'-methylanilino]uracil) and EMAU (6-[3'-ethyl-4'-methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB-EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Time-kill assays and broth dilution testing confirmed bactericidal activity. These anilinouracil derivatives represent a novel class of antimicrobials with promising activities against gram-positive bacteria that are resistant to currently available agents, validating replication-specific DNA polymerase III as a new target for antimicrobial development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • DNA Polymerase III / antagonists & inhibitors*
  • Enterococcus / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / enzymology
  • Humans
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects
  • Uracil / analogs & derivatives
  • Uracil / pharmacology*


  • 6-(3'-ethyl-4'-methylanilino)uracil
  • 6-(3'-iodo-4'-methylanilino)uracil
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Uracil
  • DNA Polymerase III