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Publication Abstract from PubMed

Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III beta subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase alpha subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.,Yin Z, Wang Y, Whittell LR, Jergic S, Liu M, Harry E, Dixon NE, Kelso MJ, Beck JL, Oakley AJ Chem Biol. 2014 Apr 24;21(4):481-7. doi: 10.1016/j.chembiol.2014.02.009. Epub, 2014 Mar 13. PMID:24631121^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.