Infectious disease burden imposed by the parasites belonging to the Trypanosomatidae family continues to represent a huge problem on people’s lives and human suffering in developing countries. Problems associated with currently available drugs are inefficient delivery, insufficient efficacy, excessive toxicity and steady loss of effectiveness due to increasing resistance. New drugs are urgently needed now and in the foreseeable future. Availability of the genome sequence of pathogens of this family offers a unique avenue for identification of novel drug targets and opportunities for the target based discoveries of new lead compounds.
By using a comparative genomic approach we have identified two common and potential targets against Trypanosomatidae family members with no human homologue to avoid potential toxicity issues. These targets, ribose isomerase and asparigine synthetase from L.major, L.infantum and T. cruzi, T. brucei were cloned and recombinant proteins expressed in bacteria systems. The enzymatic reactions to new compounds test are ongoing.
The objectives in this project will be to identify new ligands (Roy, Nilanjan team), synthesize small-ligand libraries (Costi, Paola team), test and validate them in vitro biochemical and cell based assays as well as their effect on the immune system (Cordeiro-da-Silva and Moreno, Javier teams) improve the biopharmaceutical properties of the new synthesized small molecules drug delivery systems, based on liposomal and nanoparticles formulations, specific to Trypanosomatidae will be developed (Cordeiro-da-Silva team).
If successful, this consortium expects to identify, synthesize, characterized new molecules towards Trypanosomatidae and to develop a targeted-drug delivery system protozoa specific.
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