Synthesis and Study of New Quinolineaminoethanols as Anti-Bacterial Drugs

The lack of antibiotics with a novel mode of action associated with the spread of drug resistant bacteria make the fight against infectious diseases particularly challenging. A quinoline core is found in several anti-infectious drugs, such as mefloquine and bedaquiline. Two main objectives were set...

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Bibliographic Details
Published in:Pharmaceuticals Vol. 12; no. 2; p. 91
Main Authors: Laumaillé, Pierre, Dassonville-Klimpt, Alexandra, Peltier, François, Mullié, Catherine, Andréjak, Claire, Da-Nascimento, Sophie, Castelain, Sandrine, Sonnet, Pascal
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 18.06.2019
MDPI
Series:Selected Papers from the 4th International Electronic Conference on Medicinal Chemistry
Subjects:
[CHIM]Chemical Sciences
[SDV]Life Sciences [q-bio]
Antibiotics
Antimicrobial agents
Bacteria
Chemical Sciences
Drugs
E coli
ESKAPEE bacteria
Gram-negative bacteria
Gram-positive bacteria
Infectious diseases
Life Sciences
Medicine
mycobacterium
Nosocomial infections
Pathogens
Pharmacy and materia medica
Quinoline
R
RS1-441
Staphylococcus infections
Tuberculosis
Quinoline
mycobacterium
nosocomial infections
ESKAPEE bacteria
tuberculosis
ISSN:1424-8247, 1424-8247
Online Access:Get full text
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Summary:The lack of antibiotics with a novel mode of action associated with the spread of drug resistant bacteria make the fight against infectious diseases particularly challenging. A quinoline core is found in several anti-infectious drugs, such as mefloquine and bedaquiline. Two main objectives were set in this work. Firstly, we evaluated the anti-mycobacterial properties of the previous quinolines 3, which have been identified as good candidates against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli) bacteria. Secondly, a new series 4 was designed and assessed against the same bacteria strains, taking the pair of enantiomers 3m/3n as the lead. More than twenty compounds 4 were prepared through a five-step asymmetric synthesis with good enantiomeric excesses (>90%). Interestingly, all compounds of series 3 were efficient on M. avium with MIC = 2–16 µg/mL, while series 4 was less active. Both series 3 and 4 were generally more active than mefloquine against the ESKAPEE bacteria. The quinolines 4 were either active against Gram-positive bacteria (MIC ≤ 4 µg/mL for 4c–4h and 4k/4l) or E. coli (MIC = 32–64 µg/mL for 4q–4v) according to the global lipophilicity of these compounds.
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PMCID: PMC6630482
ISSN:1424-8247
1424-8247
DOI:10.3390/ph12020091