IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The Polyamine Pathway as a Potential Therapeutic Target against Leishmaniasis
Autor/es:
PANOZZO ZENERE, ESTEBAN A; SIGRID C. ROBERTS
Lugar:
PORTLAND
Reunión:
Exposición; Oregon Bio 2013 Annual Conference, September 16th ?18th; 2013
Institución organizadora:
Oregon Bio 2013 Annual Conference, September 16th ?18th
Resumen:
To determine whether antileishmanial polyamine analogs exert their efficacy by inhibiting enzymes involved in the polyamine biosynthetic pathway 28 polyamine analogs were screened in intact L. donovani parasites and several compounds were highly effective with EC50 values around 10 ng/μl. Most compounds had the same efficacy with or without putrescine supplementation, however, at least two compounds were less toxic in the presence of putrescine, suggesting that these chemicals indeed targeted polyamine pathway enzymes ODC or ARG. 2) To determine whether arginine analogs that inhibit the recombinant enzyme arginase are effective against the Leishmania parasites. The arginine analogues NOHA and norNOHA showed moderate toxicity against intact L. donovani parasites; the boronic acid derivatives, BEC and ABH, were basically non-toxic even at high concentrations. This is surprising because these analogs are highly effective against the recombinant ARG, an essential enzyme14. We speculate that a lack of uptake is causing parasite resistance. Putrescine supplementation completely rescued parasite proliferation suggesting that NOHA and norNOHA target ARG in intact parasites Different Leishmania species exhibit disparate sensitivities toward the drugs underscoring the emerging concept that treatment choices may have to be tailored towards the specific Leishmania species