L-proline subtituted compounds as new agents against leishmaniasis and trypanosomiasis.

ESTEBAN A. PANOZZO ZENERE; MARÍA JULIA BARISÓN; BABU L. TEKWANI; ARIEL SILBER; GUILLERMO R. LABADIE

Mar del Plata, Bs. As.

Congreso; IX Congreso de Protozoología y Enfermedades Parasitarias; 2011

Sociedad Argentina de Protozoología

Chagas’disease and leishmaniasis are the most challenging public health problem for Latinamerican countries. Based on the high mortality and morbidity on these countries population, the eradication and treatment of these diseases are always on government’s agenda. Currently used chemotherapetic agents are effective only on the acute stage on the diseases with a limited efectivity on chronic stages. T. cruzi, L. donovani y T.brucei are exposed to different temperature, pH, and nutrient over their life cycle that are markedly different between the vector host and host. The parasite life depends of different mechanisms that involved morphogenesis and changes on surface protein and metabolite transport that are different from the host. T. cruzi metabolism is based on amino acids as carbon source and also as energy reservoir. Proline is the main exogenous carbon source, being also capable of used other amino acids. L donovani L-proline transport has been well characterized that is different in humans. Based on those precedents, we have prepared a collection of L-proline analogs as new chemotherapeutic agents againt trypanosomatids. These analogs have being properly derivatized on the nitrogen by “click chemistry”. Inhibition studies over L. donovani have shown promising results, being less active on T cruzi but following the same activity pattern.