Ecto-5’-nucleotidase (ecto-5’-NT, 5’-NT, eN, CD73) is a membrane ectoenzyme that is primarily responsible for the extracellular production of adenosine from AMP. Ecto-5'-NT is overexpressed in various types of cancer cells, leading to elevated concentrations of adenosine in the tumour microenvironment. Adenosine has also been found to be important in cancer pathogenesis, showing strong immunosuppressive effects over antitumour T cells and macrophages and promoting neovascularization and cell adherence. These actions support tumour growth and development. It has been suggested that the inhibition of ecto-5’-NT results in lower extracellular concentrations of adenosine within the tumour microenvironment, which would directly affect cancer cells and render malignant cells more susceptible to host defence systems. Such mechanisms are proposed to represent promising new targets for cancer therapy. The aim of this review is to explore the biochemical and structural features of ecto-5’-NT, including a brief analysis of its active site by molecular modelling, as a means of evaluating whether the inhibition of this enzyme does indeed represent a feasible strategy for treating cancer. Known inhibitors and possible prototypes that could be used to target ecto-5’-NT during cancer therapy are also discussed.

Leishmaniasis is one of the major neglected tropical diseases in the world and it is considered endemic in 88 countries. This disease is transmitted by a Leishmania spp. infected sandfly and it may lead to cutaneous or systemic manifestations. The preconized treatment has low efficacy and there are cases of resistance to some drugs. Therefore, the search for new efficient molecular targets that can lead to the preparation of new drugs must be pursued. This review aims to evaluate both Leishmania enzymes PTR1 and DHFR-TS as potential drug targets, highlight their inhibitors and to discuss critically the use of chemoinformatics to elucidate interactions and propose new molecules against these enzymes.

An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC₅₀ values of about half that of the IC₅₀ of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G₂/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.