Search of Allosteric Inhibitors and Associated Proteins of an AKT- like Kinase from Trypanosoma cruzi .

Proteins associated to the PI3K/AKT/mTOR signaling pathway are widely used targets for cancer treatment, and in recent years they have also been evaluated as putative targets in trypanosomatids parasites, such as Trypanosoma cruzi . Here, we performed a virtual screening approach to find candidates that can bind regions on or near the Pleckstrin homology domain of an AKT- like protein in T. cruzi. The compounds were also evaluated in vitro. The in silico and experimental results allowed us to identify a set of compounds that can potentially alter the intracellular signaling pathway through the AKT- like kinase of the parasite; among them, a derivative of the pyrazolopyridine nucleus with an IC ₅₀ of 14.25 ± 1.00 μM against amastigotes of T. cruzi . In addition, we built a protein⁻protein interaction network of T. cruzi to understand the role of the AKT- like protein in the parasite, and look for additional proteins that can be postulated as possible novel molecular targets for the rational design of compounds against T. cruzi .