Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 155, Issue -, Pages 705-713Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.06.045
Keywords
Halogenated quinolines; Drug discovery; Chemical synthesis; Antibacterial agents; Biofllm eradication; Staphylococcus epidermidis
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Funding
- University of Florida
- Emerging Pathogens Institute
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Antibiotic-resistant bacteria and surface-attached biofilms continue to play a significant role in human health and disease. Innovative strategies are needed to identify new therapeutic leads to tackle infections of drug-resistant and tolerant bacteria. We synthesized a focused library of 14 new halogenated quinolines to investigate the impact of ClogP values on antibacterial and biofilm-eradication activities. During these investigations, we found select polar appendages at the 2-position of the HQ scaffold were more well-tolerated than others. We were delighted to see multiple compounds display enhanced activities against the major human pathogen S. epidermidis. In particular, HQ 2 (ClogP = 3.44) demonstrated enhanced activities against MRSE 35984 planktonic cells (MIC = 0.59 mu M) compared to MRSA and VRE strains in addition to potent MRSE biofilm eradication activities (MBEC = 2.35 mu M). Several of the halogenated quinolines identified here reported low cytotoxicity against HeLa cells with minimal hemolytic activity against red blood cells. We believe that halogenated quinoline small molecules could play an important role in the development of next-generation antibacterial therapeutics capable of targeting and eradicating biofilm-associated infections. (C) 2018 Elsevier Masson SAS. All rights reserved.
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