Faustine Catherine Dubar

Publications (13) View all

• Article: Opening up the advantages of the ruthenocenic bioprobes of ferroquine: distribution and localization in Plasmodium falciparum-infected erythrocytes.

  Christophe Biot, Faustine Dubar, Jamal Khalife, Christian Slomianny
  [show abstract] [hide abstract]
  ABSTRACT: A ferrocene-quinoline conjugate named ferroquine (FQ or SSR97193) is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. FQ was shown to be efficient for the treatment of uncomplicated malaria in humans (phase IIb of clinical trials). However, the molecular basis of FQ's mechanism of action is still unknown because few approaches (such as radioactive labelling or immunofluorescence) are available for that purpose. Previous reports from our laboratory suggest that the intramolecular hydrogen bond in the lateral side chain plays a crucial role in the antimalarial activity of the drug. We used two ruthenocenic bioprobes of FQ (with and without an intramolecular hydrogen bond) to study their localization and quantification in Plasmodium falciparum-infected erythrocytes. We first used Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) analysis to trace ruthenoquine (RQ, with an intramolecular hydrogen bond) and methylruthenoquine (Me-RQ, without an intramolecular hydrogen bond) in the infected red blood cells (iRBCs). We showed that RQ accumulates faster in the digestive vacuole of the iRBCs than Me-RQ. We next examined the ruthenium distribution at the ultrastructural level by transmission electron microscopy (TEM). We showed that RQ accumulates faster in the parasitic digestive vacuole (DV) close to its membranes than Me-RQ.
  Metallomics 06/2012; 4(8):780-3. · 3.90 Impact Factor
• Article: Statistical methodology for the detection of small changes in distances by EXAFS: application to the antimalarial ruthenoquine.

  Emmanuel Curis, Faustine Dubar, Ioannis Nicolis, Simone Bénazeth, Christophe Biot
  [show abstract] [hide abstract]
  ABSTRACT: Antimalarial compounds ruthenoquine and methylruthenoquine were studied by X-ray absorption spectroscopy both in solid state and in solution, in normal (aqueous or CH(2)Cl(2) solutions) and oxidative (aqueous solution with H(2)O(2), either equimolar or in large excess) conditions, to detect small changes in the coordination sphere of the ruthenium atom. Since changes in the EXAFS spectra of these compounds are quite subtle, a complete procedure was developed to assess the different sources of uncertainties in fitted structural parameters, including the use of multivariate statistic methods for simultaneous comparison of edge energy correction ΔE(0) and distances, which can take into account the very strong correlation between these two parameters. Factors limiting the precision of distance determination depend on the recording mode. In transmission mode, the main source of uncertainty is the data reduction process, whereas in fluorescence mode, experimental noise is the main source of variability in the fitted parameters. However, it was shown that the effects of data reduction are systematic and almost identical for all compounds; hence, they can be ignored when comparing distances. Consequently, for both fluorescence and transmission recorded spectra, experimental noise is the limiting factor for distance comparisons, which leads to the use of statistical methods for comparing distances. Univariate methods, focusing on the distance only, are shown to be less powerful in detecting changes in distances than bivariate methods making a simultaneous comparison of ΔE(0) and distances. This bivariate comparison can be done either by using the Hotelling's T(2) test or by using a graphical comparison of Monte Carlo simulation results. We have shown that using these methods allows for the detection of very subtle changes in distances. When applied to ruthenoquine compounds, it suggests that the implication of the nonbinding doublet of the aminoquine nitrogen in either protonation or methylation enhances the tilt of the two cyclopentadienyls. It also suggests that ruthenoquine and methylruthenoquine are, at least partially, oxidized in the presence of H(2)O(2), with a small decrease in the Ru-C bond length and increase in the edge energy.
  The Journal of Physical Chemistry A 05/2012; 116(23):5577-85. · 2.95 Impact Factor
• Source

  Available from: sylvain bohic

  Article: Deciphering the Resistance-Counteracting Functions of Ferroquine in Plasmodium falciparum-Infected Erythrocytes.

  Faustine Dubar †, Sylvain Bohic ‡§, Daniel Dive, Yann Guérardel, Peter Cloetens §, Jamal Khalife, Christophe Biot
  ACS Med. Chem. Lett. 04/2012;
• Article: [Targeting malaria parasite at the level of apicoplast: an update].

  Christophe Biot, Cyrille Y Botté, Faustine Dubar, Eric Maréchal
  [show abstract] [hide abstract]
  ABSTRACT: In 1996, the discovery of a relic chloroplast in Plasmodium and Toxoplasma cells has strongly changed our vision of these parasites in the "Tree of Life", and has opened an unexpected new field of investigation in the search for antiparasitic treatments, including antimalarials. This review details our current understanding of the sophisticated evolution of the parasites of the Apicomplexa phylum and briefly covers a decade of research and development in drug discovery, trying to target the malaria parasite at the level of its plant-like organelle. Fifteen years after the discovery of the apicoplast and ten years after the publication of the genome of Plasmodium falciparum, it seems that we have completed a first phase of tests of available antibiotics and herbicides. In the human host, the liver phase is the only parasitic stage, for which biological functions harbored by the apicoplast, such as fatty acid biosynthesis, seem indispensable. During the erythrocytic phase, recent results have focused the attention on the processes controlling the biogenesis of the apicoplast, and one of the functions harbored by the apicoplast, i.e. the biosynthesis of isoprenoids, as major -promising targets for future treatments.
  Medecine sciences: M/S 02/2012; 28(2):163-71. · 0.64 Impact Factor
• Article: In situ nanochemical imaging of label-free drugs: a case study of antimalarials in Plasmodium falciparum-infected erythrocytes.

  Faustine Dubar, Sylvain Bohic, Christian Slomianny, Jean-Charles Morin, Patrick Thomas, Hadidjatou Kalamou, Yann Guérardel, Peter Cloetens, Jamal Khalife, Christophe Biot
  [show abstract] [hide abstract]
  ABSTRACT: We report here for the first time the in vitro localization of unlabeled antimalarial drugs with high spatial resolution. This strategy further enhances our understanding of the action mechanisms of antimalarial drugs. Our approach may be applied to a wide range of domains where quantitative chemical imaging of drugs at the sub-cellular level appears critical.
  Chemical Communications 12/2011; 48(6):910-2. · 6.17 Impact Factor