Coumarins are secondary metabolites that are widely distributed within the plant kingdom, some of which have been extensively studied for their antioxidant properties. The antioxidant activity of coumarins assayed in the present study was measured by different methods, namely the 1,1-diphenyl-2-picryl-hydrazyl (DPPH•) method, cyclic voltammetry and the antioxidant capacity against peroxyl radicals (ACAP) method. The 7,8-dihydroxy-4-methylcoumarin (LaSOM 78), 5-carboxy-7,8-dihydroxy-4-methylcoumarin (LaSOM 79), and 6,7-dihydroxycoumarin (Esculetin) compounds proved to be the most active, showing the highest capacity to deplete the DPPH radicals, the highest antioxidant capacity against peroxyl radicals, and the lowest values of potential oxidation.
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.
Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D), protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (DTT) and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II), which can be explained by the presence of chemical elements found in the constitution of pesticides. Reduced glutathione (GSH) had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA), in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids.