Curcumin (CUR) is the major constituent of the rhizomes of Curcuma longa and has been widely investigated for its chemotherapeutic properties. The well-known activity of CUR against Leishmania sp., Trypanosoma brucei and Plasmodium falciparum led us to investigate its activity against Trypanosoma cruzi. In this work, we tested the cytotoxic effects of CUR and other natural curcuminoids on different forms of T. cruzi, as well as the ultrastructural changes induced in epimastigote form of the parasite. CUR was verified as the curcuminoid with more significant trypanocidal properties (IC50 10.13 μM on epimastigotes). Demethoxycurcumin (DMC) was equipotent to CUR (IC50 11.07 μM), but bisdemethoxycurcumin (BDMC) was less active (IC50 45.33 μM) and cyclocurcumin (CC) was inactive. In the experiment with infected murine peritoneal macrophages all diarylheptanoids were more active than the control in the inhibition of the trypomastigotes release. The electron microscopy images showed ultrastructural changes associated with the cytoskeleton of the parasite, indicating tubulin as possible target of CUR in T. cruzi. The results obtained by flow cytometry analysis of DNA content of the parasites treated with natural curcuminoids suggested a mechanism of action on microtubules related to the paclitaxel`s mode of action. To better understand the mechanism of action highlighted by electron microscopy and flow cytometry experiments we performed the molecular docking of natural curcuminoids on tubulin of T. cruzi in a homology model and the results obtained showed that the observed interactions are in accordance with the IC50 values found, since there CUR and DMC perform similar interactions at the binding site on tubulin while BDMC do not realize a hydrogen bond with Lys163 residue due to the absence of methoxyl groups. These results indicate that trypanocidal properties of CUR may be related to the cytoskeletal alterations.

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This paper presents an introduction to the cellular signaling mechanism governed by the balanced action of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP) by phosphorylation / dephosphorylation of tyrosine residues in proteins. For many years PTK were the main targets for the development of anticancer drugs and today many PTK inhibitors are already widely used in the cancer treatment. Inhibitors of PTP are still in the development stage because of misconceptions about this family of enzymes. Thus, this review seeks to clarify some important points that justify the current interest in PTP as a target in cancer treatment. An introductory description of the classification is made, together with a discussion on structure and PTP mechanism of action with particular focus on SHP family composed of two PTP: SHP-1 and SHP-2. This paper discusses the effects of over expression or gain of function mutations occurred in SHP-2 in the emergence and progression of cancerous state by activation of the RAS / ERK. Finally, some SHP-2 inhibitors that have been discovered to date are presented.