Publications
Here you can view the different articles I have written or co-authored, as well as the journals in which I have reviewed articles. For each one published article you can access to the page of the journal.
Overview
Co-author of 37 scientific articles published in peer-reviewed journals and of 2 book chapters.
Reviewer of 198 articles in 38 scientific journals. In the reviewer Board / Editorial Board of 9 journals
Co-author of 63 symposium communications presented in scientific symposiums.
h-index: 14 /13 (May 2022, Google Scholar/Scopus)
Last update: May 2022.
Published Scientific Articles.
2022
37. Varied effect of fortification of kale sprouts with novel organic selenium compounds on the synthesis of sulphur and phenolic compounds in relation to cytotoxic, antioxidant and anti-inflammatory activity.
Microchemical Journal, 2022, 179, 107509. August 2022.
Paśko, P.; Galanty, A.; Zagrodzki, P.; Żmudzki, P.; Bieniek, U.; Prochownik, E.; Domínguez-Álvarez, E.; Bierła, K.; Łobiński, R.; Szpunar, J.; Handzlik, J.; Marcinkowska, M.;; Gorinstein, S.
Abstract:
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. potential for the treatment of drug-resistant cancer.
36. Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents.
Drug Resistance Updates, 2022, 63, 100844. July 2022.
Domínguez-Álvarez, E.; Rácz, B.; Marć, M.A.; Nasim, M.J.; Szemerédi, N.; Viktorová, J.; Jacob, C.; Spengler, G.
Abstract:
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.
35. Ketone-selenoesters as potential anticancer and multidrug resistance modulation agents in 2D and 3D ovarian and breast cancer in vitro models.
Scientific Reports, 2022, 12, 6548. April 2022.
Dobiasová, S.; Szemerédi, N.; Kučerová, D.; Koucká, K.; Václaviková, R.; Gbelcová, H.; Ruml, T.; Domínguez-Álvarez, E.; Spengler, G.; Viktorová, J.
Abstract:
Long-term treatment of cancer with chemotherapeutics leads to the development of resistant forms that reduce treatment options. The main associated mechanism is the overexpression of transport proteins, particularly P-glycoprotein (P-gp, ABCB1). In this study, we have tested the anticancer and multidrug resistance (MDR) modulation activity of 15 selenocompounds. Out of the tested compounds, K3, K4, and K7 achieved the highest sensitization rate in ovarian carcinoma cells (HOC/ADR) that are resistant to the action of the Adriamycin. These compounds induced oxidation stress, inhibited P-gp transport activity and altered ABC gene expression. To verify the effect of compounds, 3D cell models were used to better mimic in vivo conditions. K4 and K7 triggered the most significant ROS release. All selected selenoesters inhibited P-gp efflux in a dose-dependent manner while simultaneously altering the expression of the ABC genes, especially P-gp in paclitaxel-resistant breast carcinoma cells (MCF-7/PAX). K4, and K7 demonstrated sensitization potential in resistant ovarian spheroids. Additionally, all selected selenoesters achieved a high cytotoxic effect in 3D breast and ovarian models, which was comparable to that in 2D cultures. K7 was the only non-competitive P-gp inhibitor, and therefore appears to have considerable potential for the treatment of drug-resistant cancer.
34. Pharmaceutical and safety profile evaluation of novel selenocompounds with noteworthy anticancer activity.
Pharmaceutics, 2022, 14(2), 367. February 2022.
Marć, M.A.; Domínguez-Álvarez, E.; Latacz, G.; Doroz-Płonka, A.; Sanmartín, C.; Spengler, G.; Handzlik, J.
Abstract:
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).
33. On the use of metallic nanoparticulated catalysts for in-situ oil upgrading.
Fuel, 2022, 313, 122677. April 2022.
Simão, A.; Domínguez-Álvarez, E.; Yuan, C.; Suwaid, M.A.; Varfolomeev, M.A.; Ancheyta, J.; Al-Mishaal, O.F.; Kudryashov, S.I.; Afanasiev, I.S.; Antonenko, D.A.; Petrashov, O.V.; Dubrovin, K.A.
Abstract:
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 factorbut also for permanent upgrading of the quality of heavy and extra-heavy oil.
32. Synthesis of novel organic selenium compounds and speciation of their metabolites in biofortified kale sprouts.
Microchemical Journal, 2022, 172(A), 106962. January 2022.
Zagrodzki, P.; Paśko, P.; Domínguez-Álvarez, E.; Salardón-Jiménez, N.; Sevilla-Hernández, C.; Sanmartín, C.; Bierła, K.; Łobiński, R.; Szpunar, J.; Handzlik, J.; Jacob, C.; Bieniek, U.; Galanty, A.; Gorinstein, S.
Abstract:
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.
2021
31. Cyano- and Ketone-Containing Selenoesters as Multi-Target Compounds against Resistant Cancers.
Cancers, 2021, 13(18), 4563. September 2021.
Kincses, A.; Nové, M.; Habibullah, G.; Sevilla-Hernández, C.; Benito-Lama, M.; Alonso-Martínez, F.J.; Viktorova, J.; Spengler, G.; Domínguez-Álvarez, E.
Abstract:
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.
30. An insight into the structure of 5-spiro aromatic derivatives of imidazolidine-2,4-dione, a new group of very potent inhibitors of tumor multidrug resistance in T-lymphoma cells.
Bioorganic Chemistry, 2021, 109, 104735. April 2021.
Żesławska, E.; Kucwaj-Brysz, K.; Kincses, A.; Spengler, G.; Szymańska, E.; Czopek, A.; Marć, M.A.; Kaczor, A.; Nitek, W.; Domínguez-Álvarez, E.; Latacz, G.; Kieć-Kononowicz, K.; Handzlik, J.
Abstract:
A series of 17 arylpiperazine derivatives of the 5-spiroimidazolidine-2,4-diones (6–22) has been explored, including variations in (i) the number of aromatic rings at position 5, (ii) the length of the linker, as well as (iii) the kind and position of the linked arylpiperazine terminal fragment. Synthesis (6–16) and X-ray crystallographic studies for representative compounds (8, 10, 14 and 18) have been performed. The ability to inhibit the tumor multidrug resistance (MDR) efflux pump P-glycoprotein (P-gp, ABCB1) overexpressed in mouse T-lymphoma cells was investigated. The cytotoxic and antiproliferative actions of the compounds on both the reference and the ABCB1-overproducing cells were also examined. The pharmacophore-based molecular modeling studies have been performed. ADMET properties in vitro of selected most active derivatives (6, 11 and 12) have been determined. All compounds, excluding 18, inhibited the cancer P-gp efflux pump with higher potency than that of reference verapamil. The spirofluorene derivatives with amine alkyl substituents at position 1, and the methyl group at position 3 (6–16), occurred the most potent P-gp inhibitors in the MDR T–lymphoma cell line. In particular, compounds 7 and 12 were 100-fold more potent than verapamil. Crystallography-supported pharmacophore-based SAR analysis has postulated specific structural properties that could explain this excellent cancer MDR-inhibitory action.
2020
29. Ketone- and cyano-selenoesters to overcome efflux pump, quorum-sensing and biofilm-mediated resistance.
Antibiotics, 2020, 9(12), 896. December 2020.
Szemerédi, N.; Kincses, A.; Rehorova, K.; Hoang, L.; Salardón-Jiménez, N.; Sevilla-Hernández, C.; Viktorova, J.; Domínguez-Álvarez, E.; Spengler, G.
Abstract:
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.
28. Antimicrobial, anticancer and multidrug-resistant reversing activity of novel oxygen-, sulfur- and selenoflavones and bioisosteric analogues.
Pharmaceuticals, 2020, 13(12), 453. December 2020.
Marć, M.A.; Kincses, A.; Rácz, B.; Nasim, M.J.; Sarfraz, M.; Lázaro-Milla, C.; Domínguez-Álvarez, E.; Jacob, C.; Spengler, G.; Almendros, P.
Abstract:
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.
27. Phenothiazines and selenocompounds: A potential novel combination therapy of multidrug resistant cancer.
Anticancer Research, 2020, 40(9), 4921-4928. September 2020.
Gajdács, M.; Nové, M.; Csonka, A.; Varga, B.; Sanmartín, C.; Domínguez-Álvarez, E.; Spengler, G.
Abstract:
Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. Results: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. Conclusion: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.
26. Biofilm eradication by symmetrical selenoesters for food-borne pathogens.
Microorganisms, 2020, 8(4), 566. April 2020.
Nové, M.; Kincses, A.; Szalontai, B.; Rácz, B.; Blair, J.M.A.; González-Prádena, A.; Benito-Lama, M.; Domínguez-Álvarez, E.; Spengler, G.
Abstract:
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.
25. Hydrothermal upgrading of heavy oil in the presence of water at sub-critical, near-critical and supercritical conditions.
Journal of Petroleum Science and Engineering, 2020, 184 (2020), 106592. January 2020.
Al-Muntaser,A.A; Varfolomeev, M.A.; Suwaid, M.A.; Yuan C.; Chemodanov, A.E.; Feoktistov,D.A.; Rakhmatullin, I.Z.; Abbas, M.; Domínguez-Álvarez, E.; .Akhmadiyarov,A.A.; Klochkov, V.V.; .Amerkhanov, M.I.
Abstract:
In this study, the hydrothermal upgrading (HTU) of high sulfur-content heavy oil was investigated at sub-critical (Sub-CW), near-critical (NCW) and supercritical water (SCW) conditions. Products obtained after HTU, including gases, liquid, and coke (if formed), were analyzed to understand the upgrading performance at different conditions. At Sub-CW (200, 250, and 300 °C), 250 °C is the optimum temperature where a viscosity reduction from 2073 to 1758 mPa s was achieved with a slight removal of sulfur (mainly sulfur) and the generation of a small amount of light and non-condensable hydrocarbons in gas phase (C1–C4, isoalkanes and alkenes, H2S, CO2 and H2, etc.). At NCW (350 °C) and SCW (400 °C), heavy oil was upgraded into light oil with a significant removal of heteroatoms, an increase of saturates content, a reduction of aromatics, resins and asphaltenes contents, and a high yield of light gaseous hydrocarbons (mainly methane). Simultaneously, each SARA fraction was also greatly ameliorated: the content of light alkanes with low molecular weight in saturates was increased, diaromatics content in aromatics was increased with a reduction of polyaromatics content, aromatics-type carbon atoms in resins was increased with a decrease in aliphatic hydrocarbons. Moreover, MALDI-TOF measurements of asphaltenes show that the molecular weights of asphaltenes were reduced. All these results indicated that HTU at Sub-CW can be used for heavy oil pre-treatment (in-situ or ex-situ upgrading) considering its main effect of viscosity reduction with a small removal of heteroatoms, while HTU at NCW and SWC has a great potential in in-situ and ex-situ upgrading and oil refining as it can convert heavy oil into light oil.
2019
24. Inhibition–Disruption of Candida glabrata Biofilms: Symmetrical Selenoesters as Potential Anti-Biofilm Agents.
Microorganisms, 2019, 7(12), 664. December2019.
De la Cruz-Claure, M.L.; Cèspedes-Llave, A.A.; Ulloa, M.T.; Benito-Lama, M.; Domínguez-Álvarez, E.; Bastida, A.
Abstract:
Candida glabrata is one of the most prevalent pathogenic Candida species in dental plaque on tooth surfaces. Candida biofilms exhibit an enhanced resistance against most antifungal agents. Thus, the development of alternative more potent and effective antimicrobials is required to overcome this resistance. In this study, three novel fluorinated derivatives and nine selenoester compounds were screened as novel antifungal and antibiofilm agents against C. krusei, C. parapsilosis, and C. glabrata (N = 81 dental isolates). C. glabrata strains were susceptible only to fluorinated compounds while C. krusei, C. parapsilosis, and C. glabrata were susceptible to the action of the selenoesters. The evaluated symmetrical selenoester compounds presented very good antifungal activity against all the tested C. glabrata dental isolates (1–4 μg/mL of minimum inhibitory concentration-MIC). The most active compound (Se-5) was able to inhibit and disperse C. glabrata biofilms. These results demonstrated that selenoesters may be novel and promising biocide agents against C. glabrata clinical dental isolates.
23. Products of Sulfide/Selenite Interaction Possess Antioxidant Properties, Scavenge Superoxide-Derived Radicals, React with DNA, and Modulate Blood Pressure and Tension of Isolated Thoracic Aorta.
Oxidative Medicine and Cellular Longevity, 2019, 9847650. November2019.
Grman, M.; Misak, A.; Kurakova, L.; Brezova, V.; Cacanyiova, S.; Berenyiova, A.; Balis, P.; Tomasova, L.; Kharma, A.; Enrique Domínguez-Álvarez, E.;Chovanec, M.; Ondrias, K.
Abstract:
Selenium (Se), an essential trace element, and hydrogen sulfide (H2S), an endogenously produced signalling molecule, affect many physiological and pathological processes. However, the biological effects of their mutual interaction have not yet been investigated. Herein, we have studied the biological and antioxidant effects of the products of the H2S (Na2S)/selenite (Na2SeO3) interaction. As detected by the UV-VIS and EPR spectroscopy, the product(s) of the H2S-Na2SeO3 and H2S-SeCl4 interaction scavenged superoxide-derived radicals and reduced ⋅cPTIO radical depending on the molar ratio and the preincubation time of the applied interaction mixture. The results confirmed that the transient species are formed rapidly during the interaction and exhibit a noteworthy biological activity. In contrast to H2S or selenite acting on their own, the H2S/selenite mixture cleaved DNA in a bell-shaped manner. Interestingly, selenite protected DNA from the cleavage induced by the products of H2S/H2O2 interaction. The relaxation effect of H2S on isolated thoracic aorta was eliminated when the H2S/selenite mixture was applied. The mixture inhibited the H2S biphasic effect on rat systolic and pulse blood pressure. The results point to the antioxidant properties of products of the H2S/selenite interaction and their effect to react with DNA and influence cardiovascular homeostasis. The effects of the products may contribute to explain some of the biological effects of H2S and/or selenite, and they may imply that a suitable H2S/selenite supplement might have a beneficial effect in pathological conditions arisen, e.g., from oxidative stress.
22. Antiviral, antimicrobial and antibiofilm acticity of selenoesters and selenoanhydrides.
Molecules, 2019, 24(23), 4264. November2019.
Spengler, G.; Kincses, A.; Mosolygó, T.; Marć, M.A.; Nové, M.; Tönki, A.S.; Gajdács, M.; Sanmartín, C.; McNeil, H.E.; Blair, J.M.A.; Domínguez-Álvarez, E.*; *
Abstract:
Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.
21. The search for Histamine H4 receptor ligands with anticancer activity among novel (thio)urea derivatives.
ChemistrySelect, 2019, 4 (36), 10943-10952. September 2019.
Domínguez-Álvarez, E.*; Łażewska, D.; Szabó, Z.; Hagenow, S.; Reiner, D.; Gajdács, M.; Spengler, G.; Stark, H.; Handzlik, J.; Kieć-Kononowicz, K.*
Abstract:
A series of 33 novel (thio)urea‐containing compounds were initially designed and synthesized as potential ligands for the histamine H4 receptor (H4R). However, only 3 compounds showed a statistically significant affinity towards H4R (Ki<10 μM). Considering the structural analogy of these thioureas to previously described seleno/thiourea compounds with anticancer and/or reversal multidrug resistance action in cancer cells, selected thioureas were evaluated in in vitro cytotoxicity‐ and cancer multidrug resistance assays. The thiourea derivatives showed a good cytotoxic activity, being the compound 13 d (4‐methyl‐N‐(p‐phenylphenyl)‐piperazine‐1‐carbothiamide) the most active (IC50 = 11.9 μM). They also enhanced the cytotoxicity of the topoisomerase inhibitors topotecan and doxorubicin in a checkerboard combination assay. Compound 13 d showed the strongest synergistic effect on topotecan activity, whereas 13 c (4‐methyl‐N‐(p‐tolyl)‐piperazine‐1‐carbothiamide) was the best in combination with doxorubicin. These results can be a good starting point to design more potent and effective (thio)urea derivatives with anticancer activity.
20. Release of reactive selenium species from phthalic selenoanhydrides in the presence of hydrogen sulfide and gluthathione with implications for cancer research.
New Journal of Chemistry, 2019, 43, 11771-11783. July 2019.
Kharma, A.; Misak, A.; Grman, M.; Brezova, V.; Kurakova, L.; Baráth, P.; Jacob, C.; Chovanec, M.; Ondrias, K.; Domínguez-Álvarez, E.*
Abstract:
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 (H2Se), that can interact with cellular components, such as glutathione (GSH) and hydrogen sulfide (H2S). 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 H2S 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 O2˙− radical exerted by R-Se and its sulfur analogue (R-S) significantly increased when they were evaluated in the presence of H2S. 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.
19. Selenoesters and selenoanhydrides as novel agents against resistant breast cancer.
Anticancer Research, 2019, 39(7), 3777-3783. July 2019.
Csonka, A.; Kincses, A.; Nové, M.; Vadas, Z.; Sanmartín, C.; Domínguez-Álvarez, E.*; Spengler, G.*
Abstract:
BACKGROUND/AIM:
Selenium-containing compounds arebecoming new alternatives in experimental chemotherapy in order to overcomemultidrug resistance in cancer. The main goal of this study was to determinewhether combined treatment with new Se-compounds would increase the effect ofconventional doxorubicin chemotherapy in breast cancer cell lines.
MATERIALS AND METHODS:
Se-compounds were evaluated regardingtheir cytotoxic and apoptosis-inducing effect on MCF-7 and ATP-binding cassettesubfamily B member 1 (ABCB1)-overexpressing KCR breast cancer cell lines.Moreover, the interaction of Se-compounds with doxorubicin was assessed usingthe MTT assay.
RESULTS:
Selenoanhydride exerted a selectiveactivity towards the doxorubicin-resistant KCR cell line overexpressing ABCB1.Among the selenoesters, only ketone-containing selenoesters exerted significantcytotoxic activity against MCF-7 and KCR cell lines and the Se-compounds actedsynergistically with doxorubicin on the KCR cell line.
CONCLUSION:
The importance of the COSeCH2COCH3 andCOSeCH2CO(CH3)3 moieties for the cytotoxic and adjuvant role of Se-compoundswas highlighted.
18. Selenocompounds as novel antibacterial agents and efflux pump inhibitors.
Molecules, 2019, 24(8), 1487. April2019.
Mosolygó, T.; Kincses, A.; Csonka, A.; Tönki, A.S.; Witek, K.; Sanmartín, C.; Marć, M.A.; Handzlik, J.; Kieć-Kononowicz, K.; Domínguez-Álvarez, E.*; Spengler, G.*
Abstract:
Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogens.
17. Inorganic polysulfides and related reactive sulfur-selenium species from the perspectiva of chemistry.
Molecules, 2019, 24(7), 1359. April2019.
Kharma, A.; Grman, M.; Misak, A.; Domínguez-Álvarez, E.; Nasim, M.J.; Ondrias, K.; Chovanec, M.; Jacob, C.*
Abstract:
Polysulfides (H₂Sx) represent a class of reactive sulfur species (RSS) which includes molecules such as H₂S₂, H₂S₃, H₂S₄, and H₂S5, and whose presence and impact in biological systems, when compared to other sulfur compounds, has only recently attracted the wider attention of researchers. Studies in this field have revealed a facet-rich chemistry and biological activity associated with such chemically simple, still unusual inorganic molecules. Despite their chemical simplicity, these inorganic species, as reductants and oxidants, metal binders, surfactant-like "cork screws" for membranes, components of perthiol signalling and reservoirs for inorganic hydrogen sulfide (H₂S), are at the centre of complicated formation and transformation pathways which affect numerous cellular processes. Starting from their chemistry, the hidden presence and various roles of polysulfides in biology may become more apparent, despite their lack of clear analytical fingerprints and often murky biochemical footprints. Indeed, the biological chemistry of H₂Sx follows many unexplored paths and today, the relationship between H₂S and its oxidized H₂Sx species needs to be clarified as a matter of "unmistaken identity". Simultaneously, emerging species, such as HSSeSH and SenS8-n, also need to be considered in earnest.
16. Organoselenium compounds as novel adjuvants of chemotherapy drugs- A promising approach to fight cancer drug resistance.
Molecules, 2019, 24(2), 336. January 2019.
Spengler, G.; Gajdács, M.; Marć, M.A.; Domínguez-Álvarez, E.*; Sanmartín, C.*
Abstract:
Malignant diseases present a serious public health burden and their treatment with traditional chemotherapy cannot be considered an all-round solution, due to toxic side effects. Selenium compounds (Se-compounds) have received substantial attention in medicinal chemistry, especially in experimental chemotherapy, both as cytotoxic agents and adjuvants in chemotherapy. A checkerboard microplate method was applied to study the drug interactions of Se-compounds and clinically relevant chemotherapeutic drugs against the multidrug-resistant (MDR) subtype of mouse t-lymphoma cells overexpressing the ABCB1 transporter. Se-compounds showed synergistic interactions with chemotherapeutic agents targeting the topoisomerase enzymes or the microtubule apparatus. The ketone-containing selenoesters showed synergism at lower concentrations (1.25 µM). Most of the tested compounds interacted antagonistically with alkylating agents and verapamil. A thiophene-containing Se-compound showed synergism with all tested drugs, except cisplatin. While the exact mechanism of drug interactions is yet unknown, the potency of the selenocompounds as efflux pump inhibitors or the potentiation of their efficacy as reactive oxygen species modulators may play a role in their complementary activity against the tested MDR lymphoma cell line..
2018
15. The anticancer anc chemopreventive activity of selenocyanate-containing compounds.
Current Pharmacology Reports, 2018, 4(6), 468-481. December2018.
Ali, W.; Álvarez-Pérez, M.; Marć, M.A.; Salardón-Jiménez, N.; Handzlik, J.; Domínguez-Álvarez, E.*
Abstract:
Selenium and selenocompounds haveattracted the attention and the efforts of scientists worldwide due to theirpromising potential applications in cancer prevention and/or treatment.Different organic selenocompounds, with diverse functional groups that containselenium, have been reported to exhibit anticancer and/or chemopreventiveactivity. Among them, selenocyanates, selenoureas, selenoesters,selenium-containing heterocycles, selenium nanoparticles, selenides anddiselenides have been considered in the search for efficiency in prevention andtreatment of cancer and other related diseases. In this review, we focus ourattention on the potential applications of selenides and diselenides in cancerprevention and treatment that have been reported so far. The around 80 selenidesand diselenides selected herein as representative compounds include promisingantioxidant, prooxidant, redox-modulating, chemopreventive, anticancer,cytotoxic and radioprotective compounds, among other activities. The aim ofthis work is to highlight the possibilities that these novel organicselenocompounds can offer in an effort to contribute to inspire medicinalchemists in their search of new promising derivatives.
14. Predictionof ADME properties for selenocompounds with anticancer and efflux pumpinhibitory activity using preliminary computational method.
Acta Pharmaceutica Hungarica, 2018, 88(2), 67-74. July 2018. Article in Hungarian.
Gajdács, M.; Handzlik, J.; Sanmartín, C.; Domínguez-Álvarez, E.; Spengler, G.*
13. Organoseleniumcompounds as antitumor agents: in vitro evaluation on a colon cancer modelsystem.
Acta Pharmaceutica Hungarica, 2018, 88(2), 59-66. July 2018. Article in Hungarian.
Gajdács, M.; Handzlik, J.; Sanmartín, C.; Domínguez-Álvarez, E.; Spengler, G.*
12. Selenides and diselenides: a review of their anticancer and chemopreventiveactivity.
Molecules, 2018, 23(3), 618. March2018.
Álvarez-Pérez, M.; Ali, W.; Marć, M.A.; Handzlik, J.; Domínguez-Álvarez, E.*
Abstract:
Selenium and selenocompounds haveattracted the attention and the efforts of scientists worldwide due to theirpromising potential applications in cancer prevention and/or treatment.Different organic selenocompounds, with diverse functional groups that containselenium, have been reported to exhibit anticancer and/or chemopreventiveactivity. Among them, selenocyanates, selenoureas, selenoesters,selenium-containing heterocycles, selenium nanoparticles, selenides anddiselenides have been considered in the search for efficiency in prevention andtreatment of cancer and other related diseases. In this review, we focus ourattention on the potential applications of selenides and diselenides in cancerprevention and treatment that have been reported so far. The around 80 selenidesand diselenides selected herein as representative compounds include promisingantioxidant, prooxidant, redox-modulating, chemopreventive, anticancer,cytotoxic and radioprotective compounds, among other activities. The aim ofthis work is to highlight the possibilities that these novel organicselenocompounds can offer in an effort to contribute to inspire medicinalchemists in their search of new promising derivatives.
11. In vitro biotransformation, safety and chemopreventive action of novel 8-methoxy-purine-2,6-dione derivatives.
Applied Biochemistry and Biotechnology,2018, 184(1): 124-139, 17 June2017.
Marć, M.A.; Domínguez-Álvarez,E.; Słoczyńska, K.; Żmudzki, P.; Chłoń-Rzepa, G.; Pękala, E.*
Abstract:
Metabolic stability, mutagenicity,antimutagenicity, and the ability to scavenge free radicals of four novel8-methoxy-purine-2,6-dione derivatives (compounds 1–4) demonstrating analgesicand anti-inflammatory properties were determined. Metabolic stability wasevaluated in Cunninghamella and microsomal models, mutagenic and antimutagenicproperties were assessed using the Ames and the Vibrio harveyi tests, and freeradical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazylradical scavenging assay. In the Cunninghamella model, compound 2 did notundergo any biotransformation; whereas 3 and 4 showed less metabolic stability:1–9 and 53–88% of the parental compound, respectively, underwentbiotransformation reactions in different Cunninghamella strains. Themetabolites detected after the biotransformation of 3 and 4 were aromatichydroxylation and N-dealkylation products. On the other hand, theN-dealkylation product was the only metabolite formed in microsome assay.Additionally, these derivatives do not possess mutagenic potential in microbiologicalmodels (Vibrio harveyi and Salmonella typhimurium) considered. Moreover, allcompounds showed a strong chemopreventive activity in the modified Vibrioharveyi strains BB7X and BB7M. However, radical scavenging activity was not themechanism which explained the observed chemopreventive activity..
2017
10. The selenium-nitrogen bond as basis for reactive selenium species with pronounced antimicrobial activity.
Current Organic Synthesis, 2017, 14(8), 1082-1090. June 2017.
Rendeková, J.; Vlasáková, D.; Arsenyan, P.; Vasiljeva, J.; Nasim, M.J.; Witek,K.; Domínguez-Álvarez, E.;Żewsławska, E.; Maniková, D.; Tejchman, W.; Saleem, R.S.Z.; Rory, K.; Handzlik,J.; Chovanec, M.*
Abstract:
In biology, selenium compounds areoften associated with good reactivity and selectivity, a combination broughtabout by rather specific modifications of thiol groups in peptides, proteinsand enzymes. Among them, selenium-nitrogen-based molecules with highlyelectrophilic selenium atoms, such as selenazoles and especially selenazoliniumsalts, are of particular interest, as they react readily with their thioltargets. Ultimately, this reactivity translates into a pronounced biologicalactivity against nematodes, certain bacteria and yeast. Considering theunderlying mode(s) of action of those reactive selenium species, our datasuggests that their activity is probably associated with altered intracellularlevels of (reduced) glutathione and other cellular thiols. Since seleniumcompounds, especially selenazolinium salts, are also easy to produce,chemically stable and widely soluble, they provide an interesting lead forantimicrobial design.
9. A selective and sensitive monitoring of the OH* radical using flavonoid-modified electrodes.
Electrochimica Acta, 2017, 258(4): 228-235, 20 December 2017.
Jabeen, E.; Janjua, N.K.*; Ahmed, S.; Domínguez-Álvarez,E.; Jacob, C.
Abstract:
In the present work, three flavonoids(Fls) namely, quercetin (quer), morin (mor), and primuletin (prim) as well astheir metal; (Cu(II) and Fe(III)) complexes (M-Fls) were deposited on APTES-FTO((3-aminopropyl)triethoxysilane-fluorine doped tin oxide) electrodes. Theformation of the (M-)Fls-APTES-FTO surface was verified and characterizedthrough AT-FTIR. These surfaces were found to detect the OH radical at aconcentration as low as 2 nM using cyclic and square wave voltammetry andthe decrease in the anodic peak currents of (M-)Fls-APTES-FTO workingelectrodes could be taken as a measure of the OH radical concentration in the sample. Furthermore, acomparison of the decrease in the peak currents of (M-)Fls-APTES-FTO caused byOH to the decrease noted in the presence of 100-foldhigher concentrations of other reactive oxygen species (ROS includingsuperoxide anion, alkylperoxide anion, singlet oxygen, chlorine monoxide, andhydrogen peroxide), confirmed a high selectivity and rather insignificantinterference by other ROS of no more than 4%. Thus, this method providessignificant selectivity in the electrochemical detection of the OH radical. Among the (M-)Fls tested for hydroxylradical detection, the most sensitive ones were Fe-quer, Cu-quer and Fe-mordeposited on APTES-FTO.
8. Selenoesters and selenoanhydrides as novel multidrug resistance reversing agents: A confirmation study in a colon cancer cell line.
Bioorganic Medicinal Chemistry Letters,2017, 27(4): 797-802, 15February 2017.
Gájdács, M..; Spengler, G.; Sanmartín, C.; Marć, M.A.; Handzlik, J.; Domínguez-Álvarez, E.*
Highlights
• Active anticancer selenocompoundswere evaluated in colon adenocarcinoma cells.
• Their selective, cytotoxic,proapoptotic and MDR reversal activity were determined.
• At 2 μM, 4 compounds reversed MDR more strongly thanreference verapamil at 20 μM.
• In cytotoxicity assay in Colo320 cells, 3 compounds showed nanomolar IC50 values.
• 4 compounds triggered apoptoticevents in >60% of the gated colon cancer cells.
7. Natural selenium particles from Staphylococcus carnosus: hazards of particles with particular promise?
Journal of Hazardous Materials, 2017, 324(A), 22-30, 15February 2017
Estevam, E.C.; Griffin, S.; Nasim, M.J.; Denezhkin, P.; Schneider, R.;Lilischkis, R.; Domínguez-Álvarez,E.; Witek, K.; Latacz, G.; Keck, C.; Schäffer, K.H.;Kieć-Kononowicz, K.; Handzlik, J.; Jacob, C*.
Highlights
• Production of good quality Se nano-and microparticles (SePa) from Staphylococcus carnosus.
• Characterization of particlesusing different techniques.
• Particles are stabilized bybacterial proteins.
• Superior activity of SePacompared to milled Se particles against nematodes.
• Possible applications of SePa in Agriculture and Medicine.
2015 - 2016
2016
6. Identification of selenocompounds with promising properties to reverse multidrug resistance.
Bioorganic Medicinal Chemistry Letters,2016, 26(12):2821-4. 15 June2016.
Domínguez-Álvarez, E.*;Gájdács, M.; Spengler, G.; Palop, J.A.; Marć, M.A.; Kieć-Kononowicz, K.;Amaral, L.; Molnár, J.; Jacob, C.; Handzlik, J.; Sanmartín, C.
Highlights
• Further biological evaluations of active anticancer selenocompounds wereperformed.
• Their cytotoxicity, apoptosis induction and MDR reversal activity weredetermined.
• 4 compounds were (1.7–3.6)-fold stronger inhibitors of MDR pumps thanverapamil.
• With IC50 values below 5 μM, 4 compounds weremore cytotoxic than thioridazine.
• 4 compounds triggered apoptotic events in >80% of the examined MDRmouse cells.
5. Monocyclic and fused azines and azoles as histamine H4 receptor ligands
Current Medicinal Chemistry, 2016, 23(18): 1870-925.
Łażewska, D.; Domínguez-Álvarez,E.; Kamińska, K.; Kuder, K.; Kieć-Kononowicz, K*.
Abstract:
The histamine H4 receptorhas stood out since its discovery and identification in 2000 as an importanttarget in the search for potential new drugs for the treatment of inflammatoryand allergic diseases such as rhinitis, pruritus and asthma. Thus, in the lastdecade, both industry and academia have performed an intensive and productivesearch for new ligands of this newest subtype of histamine receptor. The mostpromising compounds found include monocyclic and fused azines, and azoles suchas bispyrimidines, di- and triaminopyrimidines, quinazolines, imidazoles,indoles, benzimidazoles and benzazoles. The aim of this review is to give aninsight into the current state of the art in the field of histamine H4receptor research, focusing mainly on the last five years.
2015
4. Nucleic acid vaccination strategies against infectious diseases.
Expert Opinion on Drug Delivery, 2015, 12 (12): 1851-65,12 September 2015.
Marć, M.A.; Domínguez-Álvarez,E.; Gamazo, C*.
Abstract
Introduction: Gene vaccines are an interesting and emergingalternative for the prevention of infectious diseases, as well as in the treatmentof other pathologies including cancer, allergies, autoimmune diseases, or evendrug dependencies. When applied to the target organism, these vaccines inducethe expression of encoded antigens and elicit the corresponding immuneresponse, with the potential ability of being able to induce antibody-, helperT cell-, and cytotoxic T cell-mediated immune responses.
Areas covered: Special attention is paid to the variety of adjuvantsthat may be co-administered to enhance and/or to modulate immune responses, andto the methods of delivery. Finally, this article reviews the efficacy data ofgene vaccines against infectious diseases released from current clinicaltrials.
Expert opinion: Taken together, this approach will have a majorimpact on future strategies for the prevention of infectious diseases.Better-designed nucleic acid constructs, novel delivery technologies, as wellas the clarification of the mechanisms for antigen presentation will improvethe potential applications of this vaccination strategy against microbialpathogens.
3. Aspects of the regulatory role of selenium salts and organic selenides in living cells with implications for drug design.
Molecules 2015, 20 (8):13894-13912, 31 July 2015.
Estevam, E.C.; Witek, K.; Faulstich, L.; Nasim, M.J.; Latacz, G.;Domínguez-Álvarez, E.; Kieć-Kononowicz, K.; Demasi, M.; Handzlik, J.; Jacob, C.
Abstract
Selenium istraditionally considered as an antioxidant element and selenium compounds areoften discussed in the context of chemoprevention and therapy. Recent studies,however, have revealed a rather more colorful and diverse biological action ofselenium-based compounds, including the modulation of the intracellular redoxhomeostasis and an often selective interference with regulatory cellularpathways. Our basic activity and mode of action studies with simple seleniumand tellurium salts in different strains of Staphylococcus aureus (MRSA) andSaccharomyces cerevisiae indicate that such compounds are sometimes notparticularly toxic on their own, yet enhance the antibacterial potential ofknown antibiotics, possibly via the bioreductive formation of insolubleelemental deposits. Whilst the selenium and tellurium compounds tested do notnecessarily act via the generation of Reactive Oxygen Species (ROS), they seemto interfere with various cellular pathways, including a possible inhibition ofthe proteasome and hindrance of DNA repair. Here, organic selenides areconsiderably more active compared to simple salts. The interference of selenium(and tellurium) compounds with multiple targets could provide new avenues forthe development of effective antibiotic and anticancer agents which may go wellbeyond the traditional notion of selenium as a simple antioxidant.
2009-2014
2014
2. Synthesis and antiproliferative activity of novel selenoesters derivatives.
European Journal of Medicinal Chemistry, 2014, 12(73): 153-66, 12 February 2014.
Domínguez-Álvarez,E.; Plano, D.; Font, M.; Calvo, A.; Prior, C.; Jacob, C.; Palop, J.A.*; Sanmartín,C.
Highlights
• 31 new selenoesters weresynthesized and their cytotoxic activity was evaluated.
• Cancer cell lines evaluated:prostate (PC-3), breast (MCF-7), lung (A-549) and colon (HT-29).
• Cytotoxic, selectivity, cyclicvoltammetry, GPx-like, DPPH activities were evaluated.
• In terms of GI50,compounds 3 and 13 were more potent than etoposide and cisplatin, respectively.
2009
1. Synthesis and pharmacological screening of several novel aroyl and heteroaroyl selenylacetic acid derivatives as cytotoxic and antiproliferative agents.
Molecules, 2009, 14: 3313-3338, 1 September 2009.
Sanmartín, C.*; Plano, D.; Domínguez,E.; Font, M.; Calvo, A.; Prior, C.; Encío, I.; Palop, J.A.
Abstract
The synthesis andcytotoxic activity of a series of twenty six aroyl and heteroaroylselenylacetic acid derivatives of general formula Ar-CO-Se-CH2-COOH orHeterar-CO-Se-CH2-COOH are reported. The synthesis was carried out by reactionof acyl chlorides with sodium hydrogen selenide, prepared in situ, and this ledto the formation of sodium aroylselenides that subsequently reacted with α-bromoacetic acid to produce the correspondingselenylacetic acid derivatives. All of the compounds were tested against aprostate cancer cell line (PC-3) and some of the more active compounds wereassessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54,HT-29, MCF-7) and one mammary gland-derived non-malignant cell line (184B5). Someof the compounds exhibited remarkable cytotoxic and antiproliferativeactivities against MCF-7 and PC-3 that were higher than those of the referencecompounds doxorubicin and etoposide, respectively. For example, in MCF-7 whenAr = phenyl, 3,5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and6.19 μM. On theother hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 μM. Furthermore, benzoylselenylacetic acid did notprovoke apoptosis nor did it perturb the cell cycle in MCF-7.
Book Chapters
2018
2. Reactive Selenium Species: redox modulation, antioxidant, antimicrobial and anticancer activities.
Organoselenium Compounds in Biology andMedicine: Synthesis, Biological and Therapeutic Treatments
Chapter 10, 277-302. United Kingdom,2018.
Editors: Vimal Kumal Jain, Indira Priyadarsini. Editorial: Royal Society ofChemistry
Nasim, M.J.; Ali, W.; Domínguez Álvarez, E.; Da Silva Júnior, E.;Saleem, R.S.Z.; Jacob, C.*
Abstract
The relationship between selenium andbiology or medicine is a rather special one. For an element that gives rise tothe amino acids selenocysteine and selenomethionine and is central to manyphysiological processes, surprisingly few selenium medications have everreached the market. Nonetheless, the past decade or two has witnessed theemergence of a new generation of biologically active and pharmaceuticallyrelevant selenium compounds, from the isolation of natural seleniumnanoparticles produced by various bacteria and the identification ofselenoneine in tuna fish to the synthesis of effective organoselenium compoundswith anticancer and antimicrobial activity based on fairly exotic seleniummotifs. This chapter therefore turns towards selenium compounds with redoxmodulating, often pro-oxidative, pro-apoptotic and eventually also lethalactions that exhibit antibacterial, antifungal, antimicrobial and anticanceractivity. These compounds include selenium nanoparticles and simple seleniumsalts, seleninic acids, selenoureas and selenoesters, but also sophisticated,multifunctional selenium-based redox catalysts which promise a uniquecombination of efficiency and selectivity. From a chemical perspective, theseagents usher in a new generation of reactive selenium compounds which providesimpetus for an amazing synthetic selenium chemistry, where multi-components aresticking and azides are clicking, while the clock for many diseases may beticking.
2013
1. Bio-Electrochemistry and Chalcogens.
Applications of Electrochemistry inMedicine, Chapter 7, 56: 249-282. New York,30 January 2013.
Series: Modern Aspects of Electrochemistry. Editor:Schlesinger, M. Editorial:Springer US
Domínguez Álvarez, E.; Viswanathan, U.M.; Burkholz, T.; Khairan, K.; Jacob, C.*
Abstract
The last couple of decades havewitnessed the emergence of the wide and diverse field of bio-electrochemistrywhich nowadays provides enough research to fill several international meetingsper year. As part of this research, topics such as the electrochemical analysisof biological samples, including electrochemical biosensors, and thecharacterization of redox properties of proteins and enzymes first come tomind. Indeed, these areas of biological electrochemistry have blossomed eversince the first pioneering studies on electrochemical biosensors in the 1980s .The field has moved on considerably since then, of course, and various aspects ofmodern biological electrochemistry have recently formed part of a special issueof ChemPhysChem .
PhD Dissertation
Diseño, síntesis y evaluación biológica de nuevos selenoésteres con actividad antiproliferativa, citotóxica y quimiopreventiva”.
Servicio de Publicaciones de la Universidad de Navarra. PhD Thesis. Universidad de Navarra, Pamplona, 2014.
Author: Enrique Domínguez-Álvarez.
Supervisors: Juan Antonio Palop-Cubillo, Carmen Sanmartín-Grijalba.
Link PhD Dissertation Dissertation in open access, available at link.
Reviewer
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