Born in 1961
Academic Training and Positions
1979-1984 Pharmacy School, Lille II University, France
1985 Approbation in Pharmacochemistry
1988 PhD degree in Pharmacochemistry, Paris XI University, France
1989 - 1990 Postdoctoral Fellow in Biochemistry, Paris 6 University, France
1990 - 1994 Junior scientist at CNRS CR2, Laboratory of Biological Chemistry, Paris 6 University
1995 - 2001 Senior scientist at CNRS CR1, Laboratory of Chemistry of Biomolecules
co-group leader of the Team “Antiparasitic drugs”
1997 Habilitation, Lille II University, France
2001 - 2002 Visiting Research Scientist, Ann Arbor, Michigan University, USA,
College of Pharmacy (Prof. Dr. G. Kenyon) and Medical School (Prof. Dr. C. Williams Jr)
since 2001 Research Director DR2 at CNRS
since 2002 Junior Group Leader at the Heidelberg University Biochemistry Center (BZH)
since 2005 Group Leader (project B14) in the collaborative research center
Sonderforschungsbereich 544 entitled "Control of tropical infectious diseases”,
since 2008 Group Leader of the bioorganic & medicinal chemistry Team, in the research unit
UMR7509 CNRS-UdS, European School of Chemistry of Polymers and Materials
(ECPM), Strasbourg University, in double affiliation with Heidelberg University at
Biochemie-Zentrum Heidelberg (BZH).
since 2008 French representative of the COST Action CM0801 “New drugs for neglected
diseases” of the EU.
New drugs against parasitic and cancer diseases are urgently and continuously needed. The aim of our interdisciplinary research is to substantiate disulfide reductase inhibitors as antiparasitic and cytostatic agents. Such compounds are active per se but, in addition, they can reverse thiol-based resistance against other drugs in parasites and tumour cells. Our strategy is based on the synthesis of mechanism-based inhibitors and subversive substrates of the selected targets, namely the glutathione reductases (GR) of the malarial parasite Plasmodium falciparum and man, the thioredoxin reductases (TrxR) of P. falciparum and man, and trypanothione reductase (TR) from Trypanosoma cruzi. The preparation of focused chemical libraries are developed in order to introduce structural diversity and to optimize the most potent inhibitors of the respective enzymes, using both classical medicinal chemistry and parallel synthesis. With the expectation of synergistic effect, double-headed prodrugs are prepared by linking bioreversibly (or not) a disulfide reductase inhibitor to a drug that is known to be directed to a specific subcellular compartment. Their effects on malarial parasites and on human cancer cell lines will be studied, with special emphasis on strains and cell lines that are resistant towards commonly used drugs in chemotherapy, i.e. the antimalarial chloroquine and the anticancer agent cis-dichlorodiamminoplatinum. These inhibitors might become of interest as antimalarial and/or as anticancer agents. The lead compounds will be produced by chemical bulk procedures and serve as candidates for in vivo experiments using mouse models. Validation of the selected targets will be achieved by correlating the molecular mode of action and the in vivo activities of the drug candidates, in particular by studying the modifications of enzyme structure and function exerted by the novel lead compounds. New compounds will be selected as potential antiparasitic or cytostatic drug candidates by the following criteria: high antiparasitic or antineoplastic activity, low toxicity against normal human cells, decrease of intracellular glutathione, thioredoxin or trypanothione levels, reversal of drug resistance, and tolerance by blood cells of persons with G6PD deficiency.
Download BZH Report Davioud-Charvet 2008-2010.