Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 44, Issue 8, Pages 2217-2221Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.44.8.2217-2221.2000
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- NIAID NIH HHS [AI41260] Funding Source: Medline
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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-3'-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 Staphylococcas 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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