In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp

ABSTRACT The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cells. This inhibitory effect increased with prolonged incubation and according to the logarithm of the drug concentration. Grepafloxacin, trovafloxacin, and ciprofloxacin were the most effective drugs, with 50% inhibitory concentrations of <10 μg/ml against both strains. Only grepafloxacin, piromidic acid, and trovafloxacin had an inhibitory effect against hepatic stages of P. falciparum and P. yoelii yoelii; this effect combined reductions of the numbers and the sizes of schizonts in treated cultures. Thus, quinolones have a potential for treatment or prevention of malaria through their unique antiparasitic effect against erythrocytic and hepatic stages of Plasmodium.

[1]  H. Webster,et al.  Measurement of Ciprofloxacin in Human Plasma, Whole Blood, and Erythrocytes by High‐Performance Liquid Chromatography , 1991, Therapeutic drug monitoring.

[2]  C. Rogier,et al.  In Vitro Activities of Antibiotics againstPlasmodium falciparum Are Inhibited by Iron , 2001, Antimicrobial Agents and Chemotherapy.

[3]  A. Sharma,et al.  In vitro activity of fluoroquinolones against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. , 1993, Indian journal of malariology.

[4]  J. Haynes,et al.  Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique , 1979, Antimicrobial Agents and Chemotherapy.

[5]  T. Gootz,et al.  Anti-Toxoplasma gondii Activities and Structure-Activity Relationships of Novel Fluoroquinolones Related to Trovafloxacin , 1999, Antimicrobial Agents and Chemotherapy.

[6]  Rafael Gozalbes,et al.  Anti-Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Techniques , 2000, Antimicrobial Agents and Chemotherapy.

[7]  T. McCutchan,et al.  Effects of interruption of apicoplast function on malaria infection, development, and transmission. , 2000, Molecular and biochemical parasitology.

[8]  W. Trager,et al.  Human malaria parasites in continuous culture. , 1976, Science.

[9]  H. Webster,et al.  An improved high-performance liquid chromatographic method for the simultaneous measurement of halofantrine and desbutylhalofantrine in human serum. , 1991, Therapeutic drug monitoring.

[10]  D. Mazier,et al.  Complete development of hepatic stages of Plasmodium falciparum in vitro. , 1985, Science.

[11]  A. Sartorelli,et al.  Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro , 1988, Antimicrobial Agents and Chemotherapy.

[12]  J. Hamzah,et al.  In vitro antimalarial activity of trovafloxacin, a fourth-generation fluoroquinolone. , 2000, Acta tropica.

[13]  W. Eling,et al.  Laser capture microdissection of Plasmodium falciparum liver stages for mRNA analysis. , 2002, Molecular and biochemical parasitology.

[14]  C. Chastang,et al.  Enzyme immunoassay to assess effect of antimicrobial agents on Toxoplasma gondii in tissue culture , 1988, Antimicrobial Agents and Chemotherapy.

[15]  Prolonged exposure of Plasmodium falciparum to ciprofloxacin increases anti-malarial activity. , 1994, The Journal of parasitology.

[16]  P. Ringwald,et al.  Assessment of pyronaridine activity in vivo and in vitro against the hepatic stages of malaria in laboratory mice. , 1999, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[17]  H. Webster,et al.  Ciprofloxacin treatment of drug-resistant falciparum malaria. , 1991, The Journal of infectious diseases.

[18]  Robert G. Ridley,et al.  Medical need, scientific opportunity and the drive for antimalarial drugs , 2002, Nature.

[19]  David S. Roos,et al.  A plastid organelle as a drug target in apicomplexan parasites , 1997, Nature.

[20]  A. Björkman,et al.  Ciprofloxacin does not achieve radical cure of Plasmodium falciparum infection in Sierra Leone. , 1992, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[21]  S. Shafran,et al.  Norfloxacin is inferior to chloroquine for falciparum malaria in northwestern Zambia: a comparative clinical trial. , 1992, The Journal of infectious diseases.