Design and synthesis of new classes of derivatives bearing antitrypanosomal and antileishmanial activity

Aimed at discovering innovative drug candidates for the treatment of trypanosomatid infections, we decided to follow two strategies that are nowadays well known in the med chem community: structure-based drug design; library design and synthesis. In the first approach, the 3D structure of validated molecular targets are used as starting point for docking simulations and de novo design. In the second approach, a compound library of 15-to-20 molecules was generated and tested by means of whole-parasite assays. In this case, the molecular target is initially unknown, and a posteriori by means of forward-chemical-genetics approaches, like the chemical proteomics, the target is tentatively fished out from parasitic cell extracts.