title: In vitro antiplasmodial activity of cepharanthine.
abstract: BACKGROUND
  New classes of anti-malarial drugs are needed to control the alarming Plasmodium falciparum resistance toward current anti-malarial therapy. The ethnopharmacological approach allows the discovery of original chemical structures from the vegetable biodiversity. Previous studies led to the selection of a bisbenzylisoquinoline, called cepharanthine and isolated from a Cambodian plant: Stephania rotunda. Cepharanthine could exert a mechanism of action different from commonly used drugs. Potential plasmodial targets are reported here.
  
  
  METHODS
  To study the mechanism of action of cepharanthine, a combined approach using phenotypic and transcriptomic techniques was undertaken.
  
  
  RESULTS
  Cepharanthine blocked P. falciparum development in ring stage. On a culture of synchronized ring stage, the comparisons of expression profiles showed that the samples treated with 5 μM of cepharanthine (IC90) were significantly closer to the initial controls than to the final ones. After a two-way ANOVA (p-value < 0.05) on the microarray results, 1,141 probes among 9,722 presented a significant differential expression.A gene ontology analysis showed that the Maurer's clefts seem particularly down-regulated by cepharanthine. The analysis of metabolic pathways showed an impact on cell-cell interactions (cytoadherence and rosetting), glycolysis and isoprenoid pathways. Organellar functions, more particularly constituted by apicoplast and mitochondrion, are targeted too.
  
  
  CONCLUSIONS
  The blockage at the ring stage by cepharanthine is described for the first time. Transcriptomic approach confirmed that cepharanthine might have a potential innovative antiplasmodial mechanism of action. Thus, cepharanthine might play an ongoing role in the progress on anti-malarial drug discovery efforts.
authors.forename: Camille
authors.initials: C
authors.lastname: Desgrouas
authors.forename: Charles
authors.initials: C
authors.lastname: Chapus
authors.forename: Jérôme
authors.initials: J
authors.lastname: Desplans
authors.forename: Christelle
authors.initials: C
authors.lastname: Travaille
authors.forename: Aurélie
authors.initials: A
authors.lastname: Pascual
authors.forename: Béatrice
authors.initials: B
authors.lastname: Baghdikian
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ollivier
authors.forename: Daniel
authors.initials: D
authors.lastname: Parzy
authors.affiliation: UMR-MD3, Institut de recherche biomédicale des armées, BP73 91223 Brétigny-sur-Orge, France. nicolas.taudon@irba.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Taudon
mesh_terms: D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D031607:Stephania / Q000737:chemistry; D052117:Benzodioxoles
chemical_list: D000962:Antimalarials; D044182:Benzylisoquinolines; C006947:cepharanthine; D052117:Benzodioxoles