Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp.
The synthesis of four new computer-designed fluoroquinolones which have been predicted by QSAR analysis to be active against the protozoa Toxoplasma gondii is described. These compounds are inhibitory in vitro for T. gondii. One of these compounds has a remarkably high activity comparable to that of trovafloxacin. It combines the basic cyclopropyl-quinoline structure of gatifloxacin or moxifloxacin with the C-7 6-amino-3-azabicyclo[3.1.0]hexyl side chain of trovafloxacin. The four compounds are also inhibitory for blood stages of Plasmodium falciparum though at high concentration. These results confirm the potential of quinolones as anti-T. gondii and antimalarial drugs but also show that the QSAR models for T. gondii cannot be reliably extended for screening antimalarial activity.
Anquetin
G
G
Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice 2, France.
Rouquayrol
M
M
Mahmoudi
N
N
Santillana-Hayat
M
M
Gozalbes
R
R
Greiner
J
J
Farhati
K
K
Derouin
F
F
Guedj
R
R
Vierling
P
P
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D005347:Fibroblasts / Q000469:parasitology; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010961:Plasmodium / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects*
D000962:Antimalarials; D000977:Antiparasitic Agents; D024841:Fluoroquinolones