Zoledronate repositioning as a potential trypanocidal drug. Trypanosoma cruzi HPRT an alternative target to be considered

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 7 million people worldwide. Considering side effects drug resistance shown current treatments, development of new anti-Chagas therapies an urgent need. T. hypoxanthine phosphoribosyltransferase (TcHPRT), key enzyme purine salvage pathway, essential for survival trypanosomatids. Previously, we assessed inhibitory effect different bisphosphonates (BPs), HPRT substrate analogues, on activity isolated enzyme. BPs are used as a treatment bone diseases growth inhibition studies have associated action with farnesyl diphosphate synthase inhibition. Here, demonstrated significant epimastigotes in presence strong correlation our previous results TcHPRT, suggesting this possible important target these drugs. We also found that parasites exhibited delay at S phase zoledronate pointing out enzymes involved cell cycle, such intracellular targets. Moreover, validated micromolar concentrations capable to interfere progression infection parasite. Altogether, findings allow us propose repositioning promising candidate against TcHPRT future rational design antiparasitic