In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria

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.