UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pharmacology and Molecular Toxicology

Publication Date

2000-8

Document Type

Article

Subjects

Anti-Bacterial Agents; DNA Polymerase III; Enterococcus; Enzyme Inhibitors; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Staphylococcus aureus; Uracil

Disciplines

Immunology and Infectious Disease | Immunoprophylaxis and Therapy | Medicinal Chemistry and Pharmaceutics

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.

Rights and Permissions

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

DOI of Published Version

10.1128/AAC.44.8.2217-2221.2000

Source

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

Journal/Book/Conference Title

Antimicrobial agents and chemotherapy

Related Resources

Link to article in PubMed

PubMed ID

10898708

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