title: Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones.
abstract: This paper reports on the rational design of a series of new 6-fluoroquinolones by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their biological evaluation against T. gondii and Plasmodium (P.) spp., and their effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6-fluoroquinolones predicted to be active against T. gondii, we succeeded in the synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy-quinolones are active on T. gondii but only one is as active as predicted. One of these four compounds appears to be an antiparasitical drug of great potential with inhibitory activities comparable to or higher than that of trovafloxacin, gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M. tuberculosis gyrase with an efficiency comparable to that of the most active quinolones but are poor inhibitors of M. tuberculosis growth.
authors.affiliation: Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Anquetin
authors.forename: Jacques
authors.initials: J
authors.lastname: Greiner
authors.forename: Nassira
authors.initials: N
authors.lastname: Mahmoudi
authors.forename: Maud
authors.initials: M
authors.lastname: Santillana-Hayat
authors.forename: Rafael
authors.initials: R
authors.lastname: Gozalbes
authors.forename: Khemais
authors.initials: K
authors.lastname: Farhati
authors.forename: Francis
authors.initials: F
authors.lastname: Derouin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aubry
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cambau
authors.forename: Pierre
authors.initials: P
authors.lastname: Vierling
mesh_terms: D000818:Animals; D015195:Drug Design; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010961:Plasmodium / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D024841:Fluoroquinolones