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Halogenated quinolines bearing polar functionality at the 2-position: Identification of new antibacterial agents with enhanced activity against Staphylococcus epidermidis
- Source :
- European Journal of Medicinal Chemistry. 155:705-713
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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 μM) compared to MRSA and VRE strains in addition to potent MRSE biofilm eradication activities (MBEC = 2.35 μM). 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.
- Subjects :
- 0301 basic medicine
Pharmacology
biology
Drug discovery
Chemistry
030106 microbiology
Organic Chemistry
Biofilm
Human pathogen
General Medicine
biology.organism_classification
Small molecule
Microbiology
HeLa
03 medical and health sciences
030104 developmental biology
Staphylococcus epidermidis
Drug Discovery
Cytotoxicity
Bacteria
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 155
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi...........167a4cd028dab7462f51807cf234ce2f