Les complexes métallo-organiques au cuivre (II), une nouvelle famille d'inhibiteurs de la protéase du virus de l'immunodéficience humaine de type 1

  • Marie Ledecq

Student thesis: Doc typesDoctor of Sciences


HIV-1 protease is a main target for the AIDS treatment, because its inhibition blocks the viral replication. De novo drug design, previously conducted in our laboratory, had pointed out several copper (II) chelates as a new family of non peptidic protease inhibitors. In order to provide a better understanding of their structure-activity relationships, we performed the physico-chemical characterization of these compounds using experimental (XRD, EPR, ESIMS)and theoretical (molecular mechanics, SIBFA method) techniques. We demonstrated that the thermodynamic stability of the complexes is an essential property to provide inhibitory activity. The SIBFA procedure adapted to copper (II) complexes helped us to study the energetics involved in the stability process. From our results, we derived a pharmacophore model describing the structural properties needed to achieve a good inhibition of the enzyme.
Date of Award16 Dec 2004
Original languageFrench
Awarding Institution
  • University of Namur
SupervisorFrancois DURANT (Supervisor), Stephane Vincent (Jury), Johan Wouters (Jury), Noah GRESH (Jury) & Michèle Ravaux (Jury)

Cite this