Quinolone-based drugs against Toxoplasma gondii and Plasmodium spp.
Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.
Anquetin
Guillaume
G
Laboratoire de Chimie Bioorganique, UMR 6001 CNRS, Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Nice Cédex 2, France.
Greiner
Jacques
J
Vierling
Pierre
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D010961:Plasmodium / Q000187:drug effects*; D011528:Protozoan Infections / Q000188:drug therapy; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014122:Toxoplasma / Q000187:drug effects*
D000981:Antiprotozoal Agents; D015363:Quinolones