title: Ketolide agents HMR 3004 and HMR 3647 (telithromycin) inhibit the growth of Plasmodium falciparum in vitro.
abstract: BACKGROUND
  Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity.
  
  
  OBJECTIVE
  The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.025-12.5 µM) for activity against chloroquine-sensitive and resistant strains of Plasmodium falciparum in vitro.
  
  
  METHODS
  The antiplasmodial activity of the two ketolide agents were determined using microscopic and colorimetric [lactate dehydrogenase assay] procedures.
  
  
  RESULTS
  Both HMR 3004 and HMR 3647 caused a dose-dependent inhibition of growth of both parasite strains with IC50 values 3 and 15 nM, respectively. Suppression of parasite growth was evident after 8 hours of exposure to both agents at 12.5 µM with total parasite clearance achieved at 40 hours.
  
  
  CONCLUSIONS
  The results indicate lack of cross-resistance between the ketolide compounds and chloroquine, implying presence of a drug target different from that of chloroquine. The particular drug target has still to be investigated but the stage-specific results indicate that it is expressed in all parasite growth phases. These observations demonstrate the anti-malarial potential of the ketolide antimicrobial agents.
authors.affiliation: Department of Medical Sciences, Public Health, Health Promotion, Faculty of Health Sciences, University of Limpopo, South Africa.
authors.forename: Marema
authors.initials: M
authors.lastname: Makgatho
authors.affiliation: Disease Surveillance and Epidemiology Unit, Provincial Department of Health, Limpopo Province, South Africa.
authors.forename: Eric
authors.initials: E
authors.lastname: Maimela
authors.affiliation: School of Anatomical Sciences, University of Witswatersrand (Wits), South Africa.
authors.forename: Felix
authors.initials: F
authors.lastname: Mbajiorgu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology; D006801:Humans; D048628:Ketolides / Q000494:pharmacology*; D008288:Malaria; D008826:Microbial Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D048628:Ketolides; C105420:RU 64004; C106791:telithromycin
keywords: Chloroquine; Plasmodium falciparum; ketolides; macrolides; malaria