Js. Daly et al., In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria, ANTIM AG CH, 44(8), 2000, pp. 2217-2221
The 6-anilinouracils are novel dGTP analogs that selectively inhibit the re
plication-specific DNA polymerase III of gram positive eubacteria. Two spec
ific derivatives, IMAU (6-[3'-iodo-3'-methylanilino]uracil) and EMAU (6- [3
'-ethyl-4'-methylanilino]uracil), were substituted with either a hydroxybut
yl (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 inhib
ited Staphylococcas aureus, coagulase-negative staphylococci, Enterococcus
faecalis, and Enterococcus faecium. Time-kill assays and broth dilution tes
ting confirmed bactericidal activity. These anilinouracil derivatives repre
sent a novel class of antimicrobials with promising activities against gram
-positive bacteria that are resistant to currently available agents, valida
ting replication-specific DNA polymerase III as a new target for antimicrob
ial development.