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 | Immunoprophylaxis and Therapy | Medicinal Chemistry and Pharmaceutics
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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DOI of Published Version
Antimicrob Agents Chemother. 2000 Aug;44(8):2217-21. doi:10.1128/AAC.44.8.2217-2221.2000. Link to article on publisher's site
Antimicrobial agents and chemotherapy
Daly JS, Giehl TJ, Brown NC, Zhi C, Wright GE, Ellison RT. (2000). In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria. Open Access Publications by UMMS Authors. https://doi.org/10.1128/AAC.44.8.2217-2221.2000. Retrieved from https://escholarship.umassmed.edu/oapubs/182