Department of Medicine; Division of Infectious Diseases and Immunology; Department of Pharmacology and Molecular Toxicology
Anti-Bacterial Agents; DNA Polymerase III; Enterococcus; Enzyme Inhibitors; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Uracil
Immunology and Infectious Disease | Pharmacology | Toxicology
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.
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Citation: Antimicrob Agents Chemother. 2000 Aug;44(8):2217-21.