title: In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA. dalyj01@ummhc.org
authors.forename: J S
authors.initials: JS
authors.lastname: Daly
authors.forename: T J
authors.initials: TJ
authors.lastname: Giehl
authors.forename: N C
authors.initials: NC
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Zhi
authors.forename: G E
authors.initials: GE
authors.lastname: Wright
authors.forename: R T
authors.initials: RT
authors.lastname: Ellison
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors*; D016983:Enterococcus / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: C413944:6-(3'-ethyl-4'-methylanilino)uracil; C413943:6-(3'-iodo-4'-methylanilino)uracil; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014498:Uracil; D004258:DNA Polymerase III