Search

Phthalic selenoanhydride (R-Se) solved in physiological buffer releases various reactive selenium species including H2Se. It is a potential compound for Se supplementation which exerts several biological effects, but its effect on the cardiovascular system is still unknown. Therefore, herein we aimed to study how R-Se affects rat hemodynamic parameters and vasoactive properties in isolated arteries. The right jugular vein of anesthetized Wistar male rats was cannulated for IV administration of R-Se. The arterial pulse waveform (APW) was detected by cannulation of the left carotid artery, enabling the evaluation of 35 parameters. R-Se (1–2 µmol kg−1), but not phthalic anhydride or phthalic thioanhydride, transiently modulated most of the APW parameters including a decrease in systolic and diastolic blood pressure, heart rate, dP/dtmax relative level, or anacrotic/dicrotic notches, whereas systolic area, dP/dtmin delay, dP/dtd delay, anacrotic notch relative level or its delay increased. R-Se (~10–100 µmol L−1) significantly decreased the tension of precontracted mesenteric, femoral, and renal arteries, whereas it showed a moderate vasorelaxation effect on thoracic aorta isolated from normotensive Wistar rats. The results imply that R-Se acts on vascular smooth muscle cells, which might underlie the effects of R-Se on the rat hemodynamic parameters.

Bioorganic Chemistry is an emerging field developing at the interface between the traditional fields of Chemistry and Biochemistry. As an interdisciplinary science, it also involves concepts from other fields, such as Physics, Biology, and Pharmacy. The field of Bioorganic Chemistry, to give a few examples (but not an exhaustive list), studies multiple different aspects, such as: the use of enzymes in synthesis; the synthesis of all types of biological molecules and biomolecules (sugars, lipids, proteins or peptides, nucleic acids, biopolymers, or their derivatives); the design and synthesis of ligands, inhibitors, or modulators of enzymes or any other cell biomolecules, cell membrane receptors, or targets; molecular recognition; biocatalysis; orthogonal synthesis; molecular and biological signaling; and informatics simulations of aspects related to cell molecules and biomolecules, both using molecular modelling and AI algorithms.

Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups.

Due to problems with selenium deficiency in humans, the search for new organic molecules containing this element in plant biofortification process is highly required. Selenium organic esters evaluated in this study (E-NS-4, E-NS-17, E-NS-71, EDA-11, and EDA-117) are based mostly on benzoselenoate scaffolds, with some additional halogen atoms and various functional groups in the aliphatic side chain of different length, while one compound contains a phenylpiperazine moiety (WA-4b). In our previous study, the biofortification of kale sprouts with organoselenium compounds (at the concentrations of 15 mg/L in the culture fluid) strongly enhanced the synthesis of glucosinolates and isothiocyanates. Thus, the study aimed to discover the relationships between molecular characteristics of the organoselenium compounds used and the amount of sulfur phytochemicals in kale sprouts. The statistical partial least square model with eigenvalues equaled 3.98 and 1.03 for the first and second latent components, respectively, which explained 83.5% of variance in the predictive parameters, and 78.6% of response parameter variance was applied to reveal the existence of the correlation structure between molecular descriptors of selenium compounds as predictive parameters and biochemical features of studied sprouts as response parameters (correlation coefficients for parameters in PLS model in the range—0.521 ÷ 1.000). This study supported the conclusion that future biofortifiers composed of organic compounds should simultaneously contain nitryl groups, which may facilitate the production of plant-based sulfur compounds, as well as organoselenium moieties, which may influence the production of low molecular weight selenium metabolites. In the case of the new chemical compounds, environmental aspects should also be evaluated.

Background/Aim: Previously, selenocompounds (Se-compounds) and in particular selenoesters have shown promising anticancer activities. Since molecular symmetry can enhance the anticancer activity, nine symmetrical selenoesters (Se-esters) have been designed as novel, potentially active anticancer agents against doxorubicin resistant breast cancer cells. Materials and Methods: To assess the biological effects of the symmetrical Se-esters, the antiproliferative activity was determined on sensitive MCF-7 and doxorubicin resistant KCR breast cancer cell lines. The interaction of the derivatives with doxorubicin was evaluated by checkerboard combination assay on KCR cells. Furthermore, apoptosis induction and ATPase activity in the presence of Se-esters were also determined on KCR cells. Results: The symmetrical derivatives showed a noteworthy antiproliferative activity, with two of them showing IC values in submicromolar concentration on MCF-7 cells. In addition, some derivatives showed selectivity towards the resistant KCR cells. The combination of most of them with doxorubicin resulted in synergistic interaction, and all Se-esters could induce early and late apoptosis in KCR cells. Finally, the compounds affected the ATPase activity of ABCB1 (P-gp). Conclusion: The symmetrical Se-esters showed potent anticancer activity, according to in vitro tests. Further research needs to be performed to obtain similar derivatives with a better activity and selectivity, and to ascertain the potential application of these Se-containing compounds using in vivo systems.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with severe effects on human health and the biosphere. Plant-based remediation offers many benefits over conventional PCB remediation, but its development has been hampered by our poor understanding of biphenyl metabolism in eukaryotes, among other factors. We report here a major PCB-responsive protein in poplar, a plant model system capable of PCB uptake and translocation. We provide structural and functional evidence that this uncharacterized protein, termed SDR57C, belongs to the heterogeneous short-chain dehydrogenase reductase (SDR) superfamily. Despite sequence divergence, structural modeling hinted at structural and functional similarities between SDR57C and BphB, a central component of the Bph pathway for biphenyl/PCB degradation in aerobic bacteria. By combining gas chromatography/mass spectrometry (GC/MS) profiling with a functional complementation scheme, we found that poplar SDR57C can replace BphB activity in the upper Bph pathway of Pseudomonas furukawaii KF707 and therefore catalyze the oxidation of 2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DHDB) to 2,3-dihydroxybiphenyl (2,3-DHB). Consistent with this biochemical activity, we propose a mechanism of action based on prior quantum studies, general properties of SDR enzymes, and the modeled docking of 2,3-DHDB to the SDR57C-NAD+ complex. The putative detoxifying capacity of SDR57C was substantiated through reverse genetics in Arabidopsis thaliana Phenotypic characterization of the SDR lines underscored an inducible plant pathway with the potential to catabolize toxic biphenyl derivatives. Partial similarities with aerobic bacterial degradation notwithstanding, real-time messenger RNA quantification indicates the occurrence of plant-specific enzymes and features. Our results may help explain differences in degradative abilities among plant genotypes and also provide elements to improve them.

Selenium deficiency in daily diet is a common problem in many countries, thus searching for new dietary sources of this trace element is an important scientific challenge. Selenium biofortified sprouts from Brassicaceae family are good candidates for new dietary selenium source, as they reveal one of the highest capability to synthesize and accumulate this element. As a part of this extensive search, the influence of novel selenium organic compounds on fortification of kale sprouts biological activity was investigated. The present study is focused on the evaluation of the influence of these compounds on the synthesis of glucosinolates, isothiocyanates, indoles and phenolic acids in kale sprouts, together with the determination of their impact on antioxidant, anti-inflammatory and cytotoxic activity on gastrointestinal, prostate, and thyroid normal and cancer cells. The present study yields the conclusion that fortification of kale sprouts with selenium organic compounds bearing benzoselenoate scaffold influences the production of isothiocyanates, phenolic acids, and enhances the antioxidant properties of fortified sprouts. Notably, fortification with compounds based on benzoselenoate scaffold display chemoprotective properties in various cancer types (gastric, thyroid, and prostate cancer). The present study can facilitate the design of future agrochemicals. Compounds bearing benzoselenoate scaffold or selenyl phenylpiperazine motif seem to be particularly promising for these purposes.

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.

An exhaustive review on the application of different metal-based nanoparticles for the upgrading of heavy oils has been performed. Particular emphasis has been put on those catalysts used for in-situ upgrading using various thermal treatment methods aiming at extracting heavy oils in a more effective manner. Different types of catalysts have been identified, such as monometallic (Mg, Al, Si, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Zr, Mo, Ce, and W), non-supported bimetallic (Ti/Zr), non-supported polymetallic (various mixtures of Co, Mo, Ni, W, Al, Zn, Cu), and supported (various metals on silica, alumina, carbon, zeolite, biogenic particles, complex inorganic and organic). Due to the great diversity of nanoparticulated catalysts (type, metal content, synthesis procedure, particle size) and evaluation conditions (experimental setup, reaction conditions, type of feed), it is not possible to make a direct comparison on their performance. Some results are highlighted on the effectiveness of the catalysts for heavy oil upgrading in terms of asphaltene adsorption, viscosity reduction, increase of API gravity, and coke formation. The reviewed literature indicates the need for more research on this topic as to develop more effective catalysts not only for increasing the recovery factor but also for permanent upgrading of the quality of heavy and extra-heavy oil.

Prior studies have reported the potent and selective cytotoxic, pro-apoptotic, and chemopreventive activities of a cyclic selenoanhydride and of a series of selenoesters. Some of these selenium derivatives demonstrated multidrug resistance (MDR)-reversing activity in different resistant cancer cell lines. Thus, the aim of this study was to evaluate the pharmaceutical and safety profiles of these selected selenocompounds using alternative methods in silico and in vitro. One of the main tasks of this work was to determine both the physicochemical properties and metabolic stability of these selenoesters. The obtained results proved that these tested selenocompounds could become potential candidates for novel and safe anticancer drugs with good ADMET parameters. The most favorable selenocompounds turned out to be the phthalic selenoanhydride (EDA-A6), two ketone-containing selenoesters with a 4-chlorophenyl moiety (EDA-71 and EDA-73), and a symmetrical selenodiester with a pyridine ring and two selenium atoms (EDA-119).

Sprouts enriched with selenium offer increased nutritional value and chemopreventive properties raising interest in their contribution to the human diet. The effect of selenium depends on its concentration and the chemical forms. The aims of this study were: to synthesize several novel organic selenium compounds (selenoesters), to examine how effectively they can deliver selenium to Brassica sprouts, and investigate their metabolism in sprouts. We revealed that selenium content in the fortified sprouts was several orders of magnitude higher than in the unfortified ones. There were significant differences between doses of selenium delivered to sprouts by different selenium compounds. A small percentage of supplemented selenium (<10%) was incorporated into the sprouts as seleno-L-methionine, Se(IV) and Se-methylselenocysteine, while several other low molecular weight selenium species were also identified, in different proportions, depending on the compound used in the fortification procedure. In conclusion: novel selenorganic compounds were successfully applied to fortify kale sprouts in selenium. The detection, screening, and characterization (including structure elucidation) of their low molecular weight metabolites and derivatives have previously been unreported in Brassica genus.

The last decade has witnessed a renewed interest in selenium (Se) as an element able to prevent a range of illnesses in humans, mainly through supplementation. However, such supplementation relies on species such as sodium selenite or selenomethionine, which proved to have limited solubility and bioavailability, thus leading to limited activity. To overcome this limitation, other selenium species need to be explored, such as phthalic selenoanhydride (R-Se), which is soluble in physiological media. R-Se releases various reactive selenium species (RSeS), including hydrogen selenide (HSe), that can interact with cellular components, such as glutathione (GSH) and hydrogen sulfide (HS). This interplay between R-Se and the cellular components provides a sophisticated biochemical release mechanism that could be behind the noteworthy biological activities observed for this compound. In order to investigate the interactions of phthalic chalcogen anhydrides with HS or GSH, we have employed UV-vis spectrophotometry, electron paramagnetic resonance spectroscopy (EPR) and plasmid DNA (pDNA) cleavage assay. We found that apart from R-Se, the other analogues do not have the ability to scavenge the cPTIO radical or to cleave pDNA on their own. In contrast, the scavenging potency for the cPTIO radical and for the O radical exerted by R-Se and its sulfur analogue (R-S) significantly increased when they were evaluated in the presence of HS. However, GSH only changed the radical scavenging activity of R-Se. These new discoveries may explain some of the biological activities associated with this class of compounds and open a new approach to ascertain the possible mechanisms underlying their biological actions.

Fifteen selenocompounds, comprising of eight ketone-containing selenoesters (K1–K8, also known as oxoselenoesters) and seven cyano-containing selenoesters (N1–N7, known also as cyanoselenoesters), have been designed, synthesized, and evaluated as novel anticancer agents. These compounds are derivatives of previously reported active selenoesters and were prepared following a three-step one-pot synthetic route. The following evaluations were performed in their biological assessment: cytotoxicity determination, selectivity towards cancer cells in respect to non-cancer cells, checkerboard combination assay, ABCB1 inhibition and inhibition of ABCB1 ATPase activity, apoptosis induction, and wound healing assay. As key results, all the compounds showed cytotoxicity against cancer cells at low micromolar concentrations, with cyanoselenoesters being strongly selective. All of the oxoselenoesters, except K4, were potent ABCB1 inhibitors, and two of them, namely K5 and K6, enhanced the activity of doxorubicin in a synergistic manner. The majority of these ketone derivatives modulated the ATPase activity, showed wound healing activity, and induced apoptosis, with K3 being the most potent, with a potency close to that of the reference compound. To summarize, these novel derivatives have promising multi-target activity, and are worthy to be studied more in-depth in future works to gain a greater understanding of their potential applications against cancer.

The invention relates to a compound of formula (I) for use in the treatment of microbial infections or colorectal cancer, wherein R1 to R4, X, n, p, q, r and s are defined in the description.

The emergence of drug-resistant pathogens leads to a gradual decline in the efficacy of many antibacterial agents, which poses a serious problem for proper therapy. Multidrug resistance (MDR) mechanisms allow resistant bacteria to have limited uptake of drugs, modification of their target molecules, drug inactivation, or release of the drug into the extracellular space by efflux pumps (EPs). In previous studies, selenoesters have proved to be promising derivatives with a noteworthy antimicrobial activity. On the basis of these results, two series of novel selenoesters were synthesized to achieve more potent antibacterial activity on Gram-positive and Gram-negative bacteria. Fifteen selenoesters (eight ketone-selenoesters and seven cyano-selenoesters) were investigated with regards to their efflux pump-inhibiting, anti-quorum-sensing (QS), and anti-biofilm effects in vitro. According to the results of the antibacterial activity, the ketone-selenoesters proved to be more potent antibacterial compounds than the cyano-selenoesters. With regard to efflux pump inhibition, one cyano-selenoester on methicillin-resistant S. aureus and one ketone-selenoester on Salmonella Typhimurium were potent inhibitors. The biofilm inhibitory capacity and the ability of the derivatives to disrupt mature biofilms were noteworthy in all the experimental systems applied. Regarding QS inhibition, four ketone-selenoesters and three cyano-selenoesters exerted a noteworthy effect on Vibrio campbellii strains.

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.

Infections caused by Salmonella species and Staphylococcus aureus represent major health and food industry problems. Bacteria have developed many strategies to resist the antibacterial activity of antibiotics, leading to multidrug resistance (MDR). The over-expression of drug efflux pumps and the formation of biofilms based on quorum sensing (QS) can contribute the emergence of MDR. For this reason, the development of novel effective compounds to overcome resistance is urgently needed. This study focused on the antibacterial activity of nine symmetrical selenoesters (Se-esters) containing additional functional groups including oxygen esters, ketones, and nitriles against Gram-positive and Gram-negative bacteria. Firstly, the minimum inhibitory concentrations of the compounds were determined. Secondly, the interaction of compounds with reference antibiotics was examined. The efflux pump (EP) inhibitory properties of the compounds were assessed using real-time fluorimetry. Finally, the anti-biofilm and quorum sensing inhibiting effects of selenocompounds were determined. The methylketone and methyloxycarbonyl selenoesters were the more effective antibacterials compared to cyano selenoesters. The methyloxycarbonyl selenoesters (Se-E2 and Se-E3) showed significant biofilm and efflux pump inhibition, and a methyloxycarbonyl selenoester (Se-E1) exerted strong QS inhibiting effect. Based on results selenoesters could be promising compounds to overcome bacterial MDR.