Synthesis and Study of New Quinolineaminoethanols as Anti-Bacterial Drugs

• Main Authors: Pierre Laumaillé, Alexandra Dassonville-Klimpt, François Peltier, Catherine Mullié, Claire Andréjak, Sophie Da-Nascimento, Sandrine Castelain, Pascal Sonnet
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Pharmaceuticals
• Subjects: Quinoline; tuberculosis; nosocomial infections; ESKAPEE bacteria; mycobacterium
• Online Access: https://www.mdpi.com/1424-8247/12/2/91

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 <b>3</b>, which have been identified as good candidates against ESKAPEE (<i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, <i>Enterobacter</i> spp. and <i>Escherichia coli</i>) bacteria. Secondly, a new series <b>4</b> was designed and assessed against the same bacteria strains, taking the pair of enantiomers <b>3m</b>/<b>3n</b> as the lead. More than twenty compounds <b>4</b> were prepared through a five-step asymmetric synthesis with good enantiomeric excesses (&gt;90%). Interestingly, all compounds of series <b>3</b> were efficient on <i>M. avium</i> with MIC = 2&#8722;16 &#181;g/mL, while series <b>4</b> was less active. Both series <b>3</b> and <b>4</b> were generally more active than mefloquine against the ESKAPEE bacteria. The quinolines <b>4</b> were either active against Gram-positive bacteria (MIC &#8804; 4 &#181;g/mL for <b>4c</b>&#8722;<b>4h</b> and <b>4k</b>/<b>4l</b>) or <i>E. coli</i> (MIC = 32&#8722;64 &#181;g/mL for <b>4q</b>&#8722;<b>4v</b>) according to the global lipophilicity of these compounds.