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Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus

Journal Article


Abstract


  • Aim: Compound 1-(4-chlorophenyl)-4,4,4-trifluoro-3-hydroxy-2-buten-1-one (compound 1) was identified as a hit against methicillin-resistant Staphylococcus aureus (MRSA) strain MW2. Methods & results: The MIC of compound 1 against MRSA was 4 μg/ml. The compound showed enhanced activity at acidic pH by lowering bacterial intracellular pH and exhibited no lysis of human red blood cells at up to 64 μg/ml and its IC 50 against HepG2 cells was 32 μg/ml. The compound reduced 1-log 10 colony forming units of intracellular MRSA in macrophages and prolonged the survival of MRSA-infected Caenorhabditis elegans (p = 0.0015) and Galleria mellonella (p = 0.0002). Conclusion: Compound 1 is a protonophore with potent in vitro and in vivo activity against MRSA and no toxicity in mammalian cells up to 8 μg/ml that warrants further investigation as a novel antibacterial.

Authors


  •   Tharmalingam, Nagendran (external author)
  •   Jayamani, Elamparithi (external author)
  •   Rajamuthiah, Rajmohan (external author)
  •   Castillo, Dawilmer (external author)
  •   Fuchs, Beth (external author)
  •   Kelso, Michael J.
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2017

Citation


  • Tharmalingam, N., Jayamani, E., Rajamuthiah, R., Castillo, D., Fuchs, B. Burgwyn., Kelso, M. J. & Mylonakis, E. (2017). Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus. Future Medicinal Chemistry, 9 (12), 1401-1411.

Scopus Eid


  • 2-s2.0-85027245424

Number Of Pages


  • 10

Start Page


  • 1401

End Page


  • 1411

Volume


  • 9

Issue


  • 12

Place Of Publication


  • United Kingdom

Abstract


  • Aim: Compound 1-(4-chlorophenyl)-4,4,4-trifluoro-3-hydroxy-2-buten-1-one (compound 1) was identified as a hit against methicillin-resistant Staphylococcus aureus (MRSA) strain MW2. Methods & results: The MIC of compound 1 against MRSA was 4 μg/ml. The compound showed enhanced activity at acidic pH by lowering bacterial intracellular pH and exhibited no lysis of human red blood cells at up to 64 μg/ml and its IC 50 against HepG2 cells was 32 μg/ml. The compound reduced 1-log 10 colony forming units of intracellular MRSA in macrophages and prolonged the survival of MRSA-infected Caenorhabditis elegans (p = 0.0015) and Galleria mellonella (p = 0.0002). Conclusion: Compound 1 is a protonophore with potent in vitro and in vivo activity against MRSA and no toxicity in mammalian cells up to 8 μg/ml that warrants further investigation as a novel antibacterial.

Authors


  •   Tharmalingam, Nagendran (external author)
  •   Jayamani, Elamparithi (external author)
  •   Rajamuthiah, Rajmohan (external author)
  •   Castillo, Dawilmer (external author)
  •   Fuchs, Beth (external author)
  •   Kelso, Michael J.
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2017

Citation


  • Tharmalingam, N., Jayamani, E., Rajamuthiah, R., Castillo, D., Fuchs, B. Burgwyn., Kelso, M. J. & Mylonakis, E. (2017). Activity of a novel protonophore against methicillin-resistant Staphylococcus aureus. Future Medicinal Chemistry, 9 (12), 1401-1411.

Scopus Eid


  • 2-s2.0-85027245424

Number Of Pages


  • 10

Start Page


  • 1401

End Page


  • 1411

Volume


  • 9

Issue


  • 12

Place Of Publication


  • United Kingdom