A set of chiral β-seleno amides were efficiently synthesized by a simple and efficient procedure involving a ring-opening reaction of 2-oxazoline with diorganyl dichalcogenides mediated by indium(I) iodide. As an application, the synthesis of selenocysteine derivatives was accomplished.
Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group -regular chow; Cholesterol group -1% cholesterolenriched diet; diphenyl diselenide group -regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group -the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral δ -aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.Hyperlipidaemia, particularly the high levels of serum cholesterol, is one of the major risk factors for atherosclerosis. Free radical-induced lipid peroxidation has been also implicated in the pathogenesis of atherosclerosis [1]. Previous studies have shown that hyperlipidaemia increases the plasma levels of reactive oxygen species, which react with lipids, proteins and DNA to produce oxidized compounds such as malondialdehyde, carbonyl proteins and 8-hydroxy-2V-deoxyguanosine, respectively [2].Fed on a cholesterol-supplemented diet, rabbits develop severe hypercholesterolaemia and increased lipid peroxidation, which leads to oxidative stress [3]. The addition of antioxidants to a diet supplemented with cholesterol has been found to decrease the levels of plasma lipid peroxidation products as well as the severity of atherosclerotic lesions in rabbits [4][5][6].Selenium is essential for the expression of several peroxidases and redox enzyme systems, like glutathione peroxidase, which protect cells from oxidative stress [7,8]. The antioxidant properties of selenium contribute to preserving health conditions and its deficiency has been linked to an increase in the incidence of oxidative stress, cardiovascular disease, immune dysfunctions, cancer, se...
Peptides comprise a versatile class of biomolecules that present a unique chemical space with diverse physicochemical and structural properties. Some classes of peptides are able to naturally cross the biological membranes, such as cell membrane and blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) and blood-brain barrier-penetrating peptides (B3PPs) have been explored by the biotechnological and pharmaceutical industries to develop new therapeutic molecules and carrier systems. The computational prediction of peptides’ penetration into biological membranes has been emerged as an interesting strategy due to their high throughput and low-cost screening of large chemical libraries. Structure- and sequence-based information of peptides, as well as atomistic biophysical models, have been explored in computer-assisted discovery strategies to classify and identify new structures with pharmacokinetic properties related to the translocation through biomembranes. Computational strategies to predict the permeability into biomembranes include cheminformatic filters, molecular dynamics simulations, artificial intelligence algorithms, and statistical models, and the choice of the most adequate method depends on the purposes of the computational investigation. Here, we exhibit and discuss some principles and applications of these computational methods widely used to predict the permeability of peptides into biomembranes, exhibiting some of their pharmaceutical and biotechnological applications.
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