Domínguez-Álvarez, E. (E.)

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2014 - 20193

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    Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides
    (MDPI AG, 2019) Kincses, A. (Annamária); Blair, J.M.A. (Jessica M. A.); Gajdács, M. (Márió); McNeil, H.E. (Helen E.); Sanmartin-Grijalba, C. (Carmen); Mosolygó, T. (Timea); Spengler, G. (Gabriella); Marc, M.A. (Malgorzata Anna); Nové, M. (Márta); Domínguez-Álvarez, E. (E.)
    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..
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    Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors
    (MDPI AG, 2019) Witek, K. (Karolina); Kincses, A. (Annamária); Kiec-Kononowicz, K. (Katarzyna); Sanmartin-Grijalba, C. (Carmen); Mosolygó, T. (Timea); Spengler, G. (Gabriella); Marc, M.A. (Malgorzata Anna); Tönki, A.S. (Ádám Szabó); Domínguez-Álvarez, E. (E.); Handzlik, J. (Jadwiga); Csonka, A. (Andrea)
    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
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    Diseño, síntesis y evaluación biológica de nuevos selenoésteres con actividad antiproliferativa, citotóxica y quimiopreventiva
    (Servicio de Publicaciones de la Universidad de Navarra, 2014) Domínguez-Álvarez, E. (E.); Palop-Cubillo, J.A. (Juan Antonio); Sanmartin-Grijalba, C. (Carmen)
    According to the antecedents found in bibliography regarding the antitumor and chemopreventive properties of certain organoselenium derivatives, it is proposed that selenocompounds which contain the selenoester functional group, following the general structure R¿CO-SeR, may possess a dual antitumor and chemopreventive activity; because these compounds could suffer an heterolytic breakdown of the selenoester bound, releasing selenium anions with capacity to take part in reductive-oxidative reactions, as well as with antiproliferative and cytotoxic properties. Thus, 51 selenoesters which contain a methyl group or a carbonyl or carboxylic functional group as R, bounded to the selenium atom directly or through and aliphatic linker have been synthesized. Meanwhile, R¿ includes an aromatic or heteroaromatic ring, monocyclic or bicyclic, substituted or no, and bounded to the selenoester carbonyl directly or through an aliphatic linker. To synthesize the compounds, the acyl chloride with the R¿ required in each case has been selenated with sodium hydrogenselenide generated in situ. Afterwards, a Sn2 reaction has been carried out, in which the selenium salt displaces the halogen of the alkyl halide which provides the desired R. In accordance with the results obtained through the biological techniques applied to evaluate the cytotoxicity and voltammetric ones used to determine the redox properties, selenoesters show the dual antitumor and in vitro chemopreventive activity against cancer predicted in the hypothesis. Regarding the chemopreventive activity of the selenoesters, all the derivatives possess redox activity for developing peaks in cyclic voltammetry when the mercury-drop electrode is used as working electrode. Alternatively, it is found that three selenoesters with aromatic or heteroaromatic difunctionalized rings with the methylselenocarbonyl moiety have nanomolar GI50 values in prostatic, colorectal, lung and breast tumour cell lines; whereas the oxopropyl 4-chlorobenzoselenoate possesses cytotoxic properties for having a LC50 in PC-3 and A549 cells at concentrations of 4.71 and 9.09 μM, respectively; four and seven fold lower than doxorubicin, the most potent reference drug considered. Abovementioned selenoesters have a certain selectivity between the PC-3 (tumour) and RWPE-1 (non-tumour) cell lines, being the dimethyl benzene-1,4-dicarboselenolate the most selective selenoester for showing a GI50 value six-fold higher in the non-cancer cells than in the tumour ones.