Lipophilic quinolone derivatives: Synthesis and in vitro antibacterial evaluation. (1st January 2022)

• Record Type: Journal Article
• Authors: Sadowski, Elodie; Bercot, Beatrice; Chauffour, Aurélie; Gomez, Catherine; Varon, Emmanuelle; Mainardis, Mary; Sougakoff, Wladimir; Mayer, Claudine; Sachon, Emmanuelle; Anquetin, Guillaume; Aubry, Alexandra
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 55(2022)
• Publication Date: 2022-01-01
• Subjects: Antibacterial -- Fluoroquinolones -- Synthesis -- Neisseria gonorrhoeae -- ESKAPE; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128450
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1 H, 13 C and 19 F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseria gonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.