title: Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine.
abstract: BACKGROUND
  Pyronaridine (PN) and chloroquine (CQ) are structurally related anti-malarial drugs with primarily the same mode of action. However, PN is effective against several multidrug-resistant lines of Plasmodium falciparum, including CQ resistant lines, suggestive of important operational differences between the two drugs.
  
  
  METHODS
  Synchronized trophozoite stage cultures of P. falciparum strain K1 (CQ resistant) were exposed to 50% inhibitory concentrations (IC50) of PN and CQ, and parasites were harvested from culture after 4 and 24 hours exposure. Global transcriptional changes effected by drug treatment were investigated using DNA microarrays.
  
  
  RESULTS
  After a 4 h drug exposure, PN induced a greater degree of transcriptional perturbation (61 differentially expressed features) than CQ (10 features). More genes were found to respond to 24 h treatments with both drugs, and 461 features were found to be significantly responsive to one or both drugs across all treatment conditions. Filtering was employed to remove features unrelated to primary drug action, specifically features representing genes developmentally regulated, secondary stress/death related processes and sexual stage development. The only significant gene ontologies represented among the 46 remaining features after filtering relate to host exported proteins from multi-gene families.
  
  
  CONCLUSIONS
  The malaria parasite's molecular responses to PN and CQ treatment are similar in terms of the genes and pathways affected. However, PN appears to exert a more rapid response than CQ. The faster action of PN may explain why PN is more efficacious than CQ, particularly against CQ resistant isolates. In agreement with several other microarray studies of drug action on the parasite, it is not possible, however, to discern mechanism of drug action from the drug-responsive genes.
authors.affiliation: National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani 12120, Thailand.
authors.forename: Kanyanan
authors.initials: K
authors.lastname: Kritsiriwuthinan
authors.forename: Sastra
authors.initials: S
authors.lastname: Chaotheing
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Chayaphat
authors.initials: C
authors.lastname: Wongsombat
authors.forename: Porntip
authors.initials: P
authors.lastname: Chavalitshewinkoon-Petmitr
authors.forename: Sumalee
authors.initials: S
authors.lastname: Kamchonwongpaisan
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000633:toxicity*; D020869:Gene Expression Profiling; D006801:Humans; D020128:Inhibitory Concentration 50; D046228:Microarray Analysis; D009287:Naphthyridines / Q000494:pharmacology / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D013312:Stress, Physiological; D013997:Time Factors
chemical_list: D000962:Antimalarials; D009287:Naphthyridines; C027871:pyronaridine