Search Results (31)

Herein, we disclose a highly efficient pathway toward 3-selenylated chromone derivatives via electrosynthesis domino C(sp²)-H bond selenylation/cyclization/deamination of 2-hydroxyaryl enaminones with diselenides. This method showed mild conditions, easy operation, a wide substrate scope, and good functional group tolerance. Furthermore, this electrosynthesis strategy was amenable to scaling up the reaction. Additionally, the preliminary experiments revealed that this reaction probably proceeded via a cation pathway instead of a radical pathway. Full article

Background: The quest for effective immunoenhancers is central to improving vaccine efficacy, especially against avian viruses such as Newcastle disease (ND) virus. Selenized polysaccharides integrate bioactive polysaccharides with selenium’s immunoenhancing properties while reducing selenium toxicity, making them promising candidates for the development of a novel vaccine immunoenhancer. Aim: This study aimed to develop an efficient selenized Brassica rapa L. polysaccharide (sBRP) and evaluate its potential to enhance the immunogenicity of a live-attenuated ND vaccine in poultry. Methods: Selenization was achieved via nitrite-assisted selenization of Brassica rapa L. polysaccharide (BRP). In vivo, 180 yellow-feathered broilers were divided into six groups: control (Con), vaccine-only (Vac), BRP (20 mg/kg), and low/medium/high-dose sBRP (sBRP-L/M/H: 5/10/20 mg/kg). On days 14 and 28, all groups except Con were vaccinated against ND via drinking water. Concurrently, the BRP and sBRP-L/M/H groups received their respective polysaccharides via oral gavage. Parameters assessed included immune organ indices, lymphocyte proliferation, serum antibody titers (HI), cytokine levels (IL-2/IL-6/IFN-γ), and densities of intestinal intraepithelial lymphocytes (IELs) and goblet cells (GCs). Results: sBRP exhibited a selenium content of 30.6 mg/g, with Se-O-C covalent modification confirmed. The sBRP-H group significantly enhanced immune organ indices, lymphocyte proliferation, Newcastle disease virus HI antibody titers, and serum IL-2/IL-6/IFN-γ levels. The sBRP-M group increased IEL and GC densities in the intestine. Conclusions: sBRP acts synergistically with the vaccine to enhance vaccine-induced cellular, humoral, and mucosal immunity, demonstrating promise as a novel oral vaccine immunoenhancer. Full article

Acrylamide, a harmful substance generated during the normal thermal treatment of foods, has been shown to adversely affect human health, particularly the vital intestinal barrier function. Meanwhile, natural polysaccharides are recognized to exert an important biofunction in the intestine by protecting barrier integrity. In this study, the non-starch, water-soluble, and nondigestive yam polysaccharide (YP) was extracted from fresh Chinese yam, while two selenylated derivatives with different extents of selenylation were prepared via the HNO₃-Na₂SeO₃ reaction system, and designated as YPSe-I and YPSe-II, respectively. Their protective activities and the associated molecular mechanisms of these substances against acrylamide-induced damage in rat intestinal epithelial (IEC-6) cells were thereby investigated. The experimental results demonstrated that the selenium contents of YPSe-I and YPSe-II were 0.80 and 1.48 g/kg, respectively, whereas that of the original YP was merely 0.04 g/kg. In IEC-6 cells, in comparison with YP, both YPSe-I and YPSe-II showed higher efficacy than YP in alleviating acrylamide-induced cell toxicity through promoting cell viability, suppressing the release of lactate dehydrogenase, and decreasing the generation of intracellular reactive oxygen species. Both YPSe-I and YPSe-II could also manifest higher effectiveness than YP in maintaining cell barrier integrity against the acrylamide-induced barrier disruption. The mentioned barrier protection was achieved by increasing transepithelial electrical resistance, reducing paracellular permeability, facilitating the distribution and expression of F-actin between the cells, and up-regulating the production of three tight junctions, namely ZO-1, occludin, and claudin-1. Additionally, acrylamide was observed to trigger the activation of the MAPK signaling pathway, thereby leading to cell barrier dysfunction. In contrast, YPSe-I and particularly YPSe-II were capable of down-regulating two MAPK-related proteins, namely p-p38 and p-JNK, and thereby inhibiting the acrylamide-induced activation of the MAPK signaling pathway. Moreover, YPSe-II in the cells was consistently shown to provide greater barrier protection than YPSe-I. In conclusion, chemical selenylation of YP could cause higher activity in mitigating acrylamide-induced cytotoxicity and intestinal barrier dysfunction, while the efficacy of activity enhancement was positively affected by the selenylation extent. Full article

Selenium compounds have garnered significant attention in the field of medicinal chemistry due to their unique biochemical properties and potential therapeutic applications for different pathologies. In this study, we report the synthesis of a new selenylated bis-pyridone compound using SeO₂ as the source of selenium. Detailed ¹H and ¹³C NMR characterizations and mass spectral analysis are given. Full article

Herein, a green biocatalytic approach using lipase as a catalyst has been developed for the synthesis of 3-selanyl-isoflavones through the selenylation/cyclization of 2-hydroxyphenyl enaminones and diphenyl di-selenide under mild conditions. The environmentally friendly method reached high yields of 87–95% in a short time at 30 °C, with 17 examples of 3-selanyl-isoflavones successfully prepared. Furthermore, we have investigated the possible mechanisms underlying this reaction. Full article

In this study, the soluble, but non-digestible, longan (Dimocarpus longan Lour.) polysaccharides (LP) were extracted from dried longan fruits and then chemically selenylated to produce two selenylated products, namely SeLP1 and SeLP2, with different selenylation extents. The aim was to investigate their protective effects on rat intestinal epithelial (IEC-6) cells exposed to the food toxin fumonisin B1 (FB1). LP only contained total Se content of less than 0.01 g/kg, while SeLP1 and SeLP2 were measured with respective total Se content of up to 1.46 and 4.79 g/kg. The cell viability results showed that these two selenylated products were more efficient than LP in the IEC-6 cells in alleviating FB1-induced cell toxicity, suppressing lactate dehydrogenase (LDH) release, and decreasing the generation of intracellular reactive oxygen species (ROS). These two selenylated products were also more effective than LP in combating FB1-induced barrier disruption via increasing the transepithelial electric resistance (TEER), reducing the paracellular permeability, decreasing the mitochondrial membrane potential (MMP) loss, and maintaining cell barrier integrity by upregulating the tight-junction-related genes and proteins. FB1 caused cell oxidative stress and barrier dysfunction by activating the MAPK and mitochondrial apoptosis signaling pathways, while SeLP1 and SeLP2 could regulate the tMAPK- and apoptosis-related proteins to suppress the FB1-mediated activation of the two pathways. Overall, SeLP2 was observed to be more active than SeLP1 in the IEC-6 cells. In conclusion, the chemical selenylation of LP caused an activity enhancement to ameliorate the FB1-induced cell cytotoxicity and intestinal barrier disruption. Meanwhile, the increased selenylation of LP would endow the selenylated product SeLP2 with more activity. Full article

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research. Full article

Sulfoxides and selenoxides oxidize thiols to disulfides while being reduced back to sulfides and selenides. While the reduction mechanism of sulfoxides to sulfides has been thoroughly explored experimentally as well as computationally, less attention has been devoted to the heavier selenoxides. In this work, we explore the reductive mechanism of dimethyl selenoxide, as an archetypal selenoxide and, for the sake of comparison, the reductive mechanism of dimethyl sulfoxide to gain insight into the role of the chalcogen on the reaction substrate. Particular attention is devoted to the key role of sulfurane and selenurane intermediates. Moreover, the capacity of these system to oxidize selenols rather than thiols, leading to the formation of selenyl sulfide bridges, is explored in silico. Notably, this analysis provides molecular insight into the role of selenocysteine in methionine sulfoxide reductase selenoenzyme. The activation strain model of chemical reactivity is employed in the studied reactions as an intuitive tool to bridge the computationally predicted effect of the chalcogen on the chalcogenoxide as well as on the chalcogenol. Full article

The process by which cancer cells evade or inhibit apoptosis is considered one of the characteristics of cancer. The ability of cancer cells to escape apoptosis contributes to tumor proliferation and promotes metastasis. The discovery of new antitumor agents is essential for cancer treatment due to the lack of selectivity of drugs and cellular resistance to anticancer agents. Several studies showed that macroalgae produce various metabolites with different biological activities among marine organisms. This review discusses multiple metabolites extracted from macroalgae and their pro-apoptotic effects through regulating apoptosis signaling pathway target molecules and the structure-activity relationship. Twenty-four promising bioactive compounds have been reported, where eight of these compounds exhibited values of maximum inhibitory concentration (IC50) of less than 7 μg/mL. Fucoxanthin was the only carotenoid reported that induced apoptosis in HeLa cells with an IC50 below 1 µg/mL. Se-PPC (a complex of proteins and selenylated polysaccharides) is the magistral compound because it is the only one with an IC50 of 2.5 µg/mL which regulates the primary proteins and critical genes of both apoptosis pathways. Therefore, this review will help provide the basis for further studies and the development of new anticancer drugs, both as single agents and adjuvants, decreasing the aggressiveness of first-line drugs and offering patients better survival and quality of life. Full article

In this work, we achieved a C3-selenylation of pyrido[1,2-a]pyrimidin-4-ones using an electrochemically driven external oxidant-free strategy. Various structurally diverse seleno-substituted N-heterocycles were obtained in moderate to excellent yields. Through radical trapping experiments, GC-MS analysis and cyclic voltammetry study, a plausible mechanism for this selenylation was proposed. Full article

Dichalcogenides (disulfides and diselenides), as reactants for organic transformations, are important and widely used because of their potential to react with nucleophiles, electrophilic reagents, and radical precursors. In recent years, in combination with photochemical technology, the application of dichalcogenides as stable radical reagents has opened up a new route to the synthesis of various sulfur- and selenium-containing compounds. In this paper, synthetic strategies for disulfides and diselenides and their applications with photochemical technology are reviewed: (i) Cyclization of dichalcogenides with alkenes and alkynes; (ii) direct selenylation/sulfuration of C−H/C−C/C−N bonds; (iii) visible-light-enabled seleno- and sulfur-bifunctionalization of alkenes/alkynes; and (iv) Direct construction of the C(sp)–S bond. In addition, the scopes, limitations, and mechanisms of some reactions are also described. Full article

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia. Full article

The Pd/Cu-catalyzed Sonogashira reaction of (E,E)-bis(2-bromovinyl) selenide and (E,E)-bis(1-bromo-1-hexen-2-yl) selenide with terminal alkynes was found to proceed at room temperature involving both bromine atoms and the selanyl function. As a result, new bis-(1,3-enynyl) selenides and enediyne hydrocarbons are formed with a complete retention of the stereoconfiguration of the initial selenides. Due to steric hindrances in the cross-coupling at the selenyl function in the case of (E,E)-bis(1-bromo-1-hexen-2-yl) selenide, the second process is realized to a lesser extent than with unsubstituted (E,E)-bis(2-bromovinyl) selenide. Full article

The anti-cancer effects of selenylated plant polysaccharides are a focus of research. As a natural plant with extensive biological effects, there have been few studies related to edible purslane (Portulaca oleracea L.). Thus, in this study, soluble P. oleracea polysaccharides (PPS) were extracted from the dried P. oleracea and then selenylated chemically using the HNO₃-Na₂SeO₃ method to obtain two selenylated products, namely, SePPS1 and SePPS2. Compared with the extracted PPS, SePPS1 and SePPS2 had much higher Se contents (840.3 and 1770.5 versus 66.0 mg/kg) while also showing lower contents in three saccharides—arabinose, fucose, and ribose—and higher contents in seven saccharides including galactose, glucose, fructose, mannose, rhamnose, galacturonic acid, and glucuronic acid, but a stable xylose content demonstrated that the performed chemical selenylation of PPS led to changes in monosaccharide composition. Moreover, SePPS1 and SePPS2 shared similar features with respect to monosaccharide composition and possessed higher bioactivity than PPS in human colon cancer HCT-116 cells. Generally, SePPS1 and SePPS2 were more active than PPS with respect to cell growth inhibition, the alteration of cell morphology, disruption of mitochondrial membrane potential, intracellular reactive oxygen species (ROS) generation, the induction of cell apoptosis, and upregulation or downregulation of five apoptosis-related genes and proteins such as Bax, Bcl-2, caspases-3/-9, and cytochrome C, that cause cell apoptosis and growth suppression via the ROS-mediated mitochondrial pathway. SePPS2 consistently showed the highest capacity to exert these observed effects on the targeted cells, suggesting that the performed chemical selenylation of PPS (in particular when higher degrees of selenylation are reached) resulted in an increase in activity in the cells. It can thus be concluded that the performed selenylation of PPS was able to incorporate inorganic Se into the final PPS products, changing their monosaccharide composition and endowing them with enhanced nutraceutical and anti-cancer effects in the colon. Full article

In the past decade, selenocyclization has been extensively exploited for the preparation of a wide range of selenylated heterocycles with versatile activities. Previously, selenium electrophile-based and FeCl₃-promoted methods were employed for the synthesis of selenylated benzoxazines. However, these methods are limited by starting material availability and low atomic economy, respectively. Inspired by the recent catalytic selenocyclization approaches based on distinctive pathways, we rationally constructed an efficient and greener double-redox catalytic system for the access to diverse selenylated benzoxazines. The coupling of I₂/I⁻ and Fe³⁺/Fe²⁺ catalytic redox cycles enables aerial O₂ to act as the driving force to promote the selenocyclization. Control and test redox experiments confirmed the roles of each component in the catalytic system, and a PhSeI-based pathway is proposed for the selenocyclization process. Full article