4mjq Citations

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs.

Chem. Biol. 21 481-7 (2014)
Related entries: 4mjr, 4mjp

Cited: 11 times
EuropePMC logo PMID: 24631121

Abstract

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 β 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 α 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.

Reviews citing this publication (2)

  1. Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs. Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta S. Br. Med. Bull. 118 138-148 (2016)
  2. Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs. Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta S. Br. Med. Bull. 118 138-148 (2016)

Articles citing this publication (9)

  1. Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis. Maitra A, Bates S, Kolvekar T, Devarajan PV, Guzman JD, Bhakta S. Int. J. Infect. Dis. 32 50-55 (2015)
  2. Congresses TB Summit 2014: prevention, diagnosis, and treatment of tuberculosis-a meeting report of a Euroscicon conference. Maitra A, Bhakta S. Virulence 5 638-644 (2014)
  3. The Influence of Efflux Pump Inhibitors on the Activity of Non-Antibiotic NSAIDS against Gram-Negative Rods. Laudy AE, Mrowka A, Krajewska J, Tyski S. PLoS ONE 11 e0147131 (2016)
  4. In vitro antibacterial activity of meclofenamate metal complexes with Cd(II), Pb(II), Co(II), and Cu(II). Crystal structures of [Cd(C14H10NO2Cl2)2∙(CH3OH)]n and [Cu(C14H10NO2Cl2)2(C5H5N)2]. Palacios-Hernández T, Höpfl H, Sánchez-Salas JL, González-Vergara E, Pérez-Benítez A, Quiroz-Alfaro MA, Méndez-Rojas MA. J. Inorg. Biochem. 139 85-92 (2014)
  5. Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis. Thomas SM, Purmal A, Pollastri M, Mensa-Wilmot K. Sci Rep 6 32083 (2016)
  6. Research Support, Non-U.S. Gov't Tackling tuberculosis: Insights from an international TB Summit in London. Maitra A, Danquah CA, Scotti F, Howard TK, Kamil TK, Bhakta S. Virulence 6 661-672 (2015)
  7. Antimicrobial synergy between carprofen and doxycycline against methicillin-resistant Staphylococcus pseudintermedius ST71. Brochmann RP, Helmfrid A, Jana B, Magnowska Z, Guardabassi L. BMC Vet. Res. 12 126 (2016)
  8. Structural insight into β-Clamp and its interaction with DNA Ligase in Helicobacter pylori. Pandey P, Tarique KF, Mazumder M, Rehman SA, Kumari N, Gourinath S. Sci Rep 6 31181 (2016)
  9. Structure of the sliding clamp from the fungal pathogen Aspergillus fumigatus (AfumPCNA) and interactions with Human p21. Marshall AC, Kroker AJ, Murray LA, Gronthos K, Rajapaksha H, Wegener KL, Bruning JB. FEBS J. 284 985-1002 (2017)