Evaluation of the (in vivo) efficacy of a novel class of broad-spectrum fungicidal compounds.

An extensive screening procedure in collaboration with CD3/CISTIM, KU Leuven was initiated and led to the discovery of a novel class of fungicidal compounds - Mid June 2008 a first priority patent application was filed claiming the first medical use of this novel fungicidal compound class. The current project aims at further studying the novel fungicidal class of molecules. The main objective is to obtain within 1 year the in vivo proof-of-concept for antifungal activity of 1 or 2 lead molecules, as well as to unravel their mode of antifungal action. To this end, following activities will be pursued: 1. Chemical synthesis of 50-200 novel analogs; 2. In vitro evaluation of analogs regarding their (a) antifungal activity, (b) toxicity and (c) stability; 3. In vivo evaluation of the efficacy and toxicity of 10-20 selected molecules, based on a C. elegans model for Candida infection; 4. In vivo evaluation of the efficacy of 1 or 2 analogs in rodent models for Candida and/or Aspergillus infection; 5. Unraveling of the mode of action of this class of molecules.

Keywords:Broad-spectrum fungicidal compounds.

Disciplines:Microbiology, Systems biology, Laboratory medicine