Arylseleninic acid as a green, bench-stable selenylating agent: synthesis of selanylanilines and 3-selanylindoles.

Arylseleninic acids were used as an electrophilic selenium source in aromatic substitution reactions, using N,N-substituted anilines and indoles as nucleophiles at 70 °C for 6-15 h. A total of fourteen 4-selanylanilines and five 3-selanylindoles were selectively obtained in good to excellent yields. The starting benzeneseleninic acids are easily prepared from the respective diselenides, are bench stable and easy to handle, affording water as the only waste at the end of the reaction.

Selenium-containing indolyl compounds: Kinetics of reaction with inflammation-associated oxidants and protective effect against oxidation of extracellular matrix proteins.

Activated white blood cells generate multiple oxidants in response to invading pathogens. Thus, hypochlorous acid (HOCl) is generated via the reaction of myeloperoxidase (from neutrophils and monocytes) with hydrogen peroxide, and peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent is formed from superoxide radicals and nitric oxide, generated by stimulated macrophages. Excessive or misplaced production of these oxidants has been linked to multiple human pathologies, including cardiovascular disease. Atherosclerosis is characterized by chronic inflammation and the presence of oxidized materials, including extracellular matrix (ECM) proteins, within the artery wall. Here we investigated the potential of selenium-containing indoles to afford protection against these oxidants, by determining rate constants (k) for their reaction, and quantifying the extent of damage on isolated ECM proteins and ECM generated by human coronary artery endothelial cells (HCAECs). The novel selenocompounds examined react with HOCl with k 0.2-1.0 × 108M-1s-1, and ONOOH with k 4.5-8.6 - × 105M-1s-1. Reaction with H2O2 is considerably slower (k < 0.25M-1s-1). The selenocompound 2-phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine provided protection to human serum albumin (HSA) against HOCl-mediated damage (as assessed by SDS-PAGE) and damage to isolated matrix proteins induced by ONOOH, with a concomitant decrease in the levels of the biomarker 3-nitrotyrosine. Structural damage and generation of 3-nitroTyr on HCAEC-ECM were also reduced. These data demonstrate that the novel selenium-containing compounds show high reactivity with oxidants and may modulate oxidative and nitrosative damage at sites of inflammation, contributing to a reduction in tissue dysfunction and atherogenesis.

Ultrasound-promoted copper-catalyzed synthesis of bis-arylselanyl chrysin derivatives with boosted antioxidant and anticancer activities.

Herein we report the use of ultrasonic irradiation (US) in the synthesis of six new semi-synthetic selenium-containing chrysin derivatives by a simple and effective methodology utilizing CuI as catalyst, in good to excellent yields (60-89%). It was observed that US accelerates the reaction compared to conventional heating with excellent selectivity for diselenylated products. Compounds were tested for their antioxidant and anticancer activities in vitro and it was observed that the presence of selenium in the A-ring of chrysin enhanced both antioxidant and anticancer properties. Semi-synthetic 6,8-bis(o-tolylselanyl)-chrysin 3b has the best radical scavenging activity of DPPH (Imax: 39.79µM) and ABTS+ (IC50: 6.5µM) radicals. Similarly, in the Reactive Species (RS) assay, 3b showed high antioxidant activity in mice cortex (IC50: 5.67µM), whereas 6,8-bis(p-anisoylselanyl)-chrysin 3c was the more active in the hippocampus (IC50: 5.63µM). The Se-chrysins were effective in prevention of lipid peroxidation, highlighting 6,8-bis(p-fluorophenylselanyl)-chrysin 3d in cortex (IC50: 0.54µM) and 3b in hippocampus (IC50: 0.27µM). In addition, 3d was effective in inhibiting human lung adenocarcinoma (A549) cells growth, with a IC50 of 19.9µM after 72h of treatment, while 6,8-bis(p-anisoylselanyl)-chrysin 3c presented the higher antiproliferative activity after 48h of treatment (IC50 of 41.4µM).