1. QM-CSA: a novel quantum mechanics-based protocol for evaluation of the carcinogen-scavenging activity of polyphenolic compoundsVeronika Furlan, Jelena Tošović, Urban Bren, 2024, izvirni znanstveni članek Opis: In this study, a novel quantum mechanics-based protocol for the evaluation of carcinogenscavenging activity (QM-CSA) is developed. The QM-CSA protocol represents a universal and
quantitative approach to evaluate and compare the activation-free energies for alkylation reactions
between individual polyphenolic compounds and chemical carcinogens of the epoxy type at physiological conditions by applying two scales: the absolute scale allowing for the comparison with
guanine and the relative scale allowing the comparison with glutathione as a reference compound.
The devised quantum mechanical methodology was validated by comparing the activation-free
energies calculated with 14 DFT functionals in conjunction with two implicit solvation models (SMD
and CPCM) and the experimental activation-free energies for reactions between nine investigated
chemical carcinogens and guanine. According to the obtained results, the best agreement with experimental data was achieved by applying DFT functionals M11-L and MN12-L in conjunction with the
flexible 6-311++G(d,p) basis set and implicit solvation model SMD, and the obtained uncertainties
were proven to be similar to the experimental ones. To demonstrate the applicability of the QM-CSA
protocol, functionals M11-L, and MN12-L in conjunction with the SMD implicit solvation model were
applied to calculate activation-free energies for the reactions of nine investigated chemical carcinogens
of the epoxy type with three catechins, namely EGCG, EGC, and (+)-catechin. The order of CSA in
this series of catechins in comparison to guanine and glutathione was determined as (+)-catechin >
EGC > EGCG. The obtained results, for the first time, demonstrated the evaluation and comparison
of CSA in a series of selected catechins with respect to glutathione and guanine. Moreover, the
presented results provide valuable insights into the reaction mechanisms and configurations of the
corresponding transition states. The novel QM-CSA protocol is also expected to expand the kinetic
data for alkylation reactions between various polyphenolic compounds and chemical carcinogens of
the epoxy type, which is currently lacking in the scientific literature
Ključne besede: activation-free energies, chemical carcinogens, polyphenols, guanine, glutathione, quantum mechanical calculations, M11-L and MN12-L DFT functionals
Objavljeno v DKUM: 04.09.2024; Ogledov: 39; Prenosov: 20
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2. A monocarbonyl curcuminoid derivative inhibits the activity of human glutathione transferase A4-4 and chemosensitizes glioblastoma cells to temozolomideSteliana Tsouri, Evanthia Tselo, Georgios E. Premetis, Veronika Furlan, Panagiota D. Pantiora, Barbara Mavroidi, Dimitris Matiadis, Maria Pelecanou, Anastassios C. Papageorgiou, Urban Bren, Marina Sagnou, Nikolaos E. Labrou, 2024, izvirni znanstveni članek Ključne besede: chemosensitization, chemoresistance, curcumin, glioblastoma, human glutathione transferase A4-4, ellagic acid, monocarbonyl curcumin derivatives, GST inhibition, temozolomide sensitization
Objavljeno v DKUM: 23.08.2024; Ogledov: 66; Prenosov: 11
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3. Monocarbonyl Curcumin Analogues as Potent Inhibitors against Human Glutathione Transferase P1-1Panagiota D. Pantiora, Veronika Furlan, Dimitris Matiadis, Barbara Mavroidi, Fereniki Perperopoulou, Anastassios C. Papageorgiou, Marina Sagnou, Urban Bren, Maria Pelecanou, Nikolaos E. Labrou, 2023, izvirni znanstveni članek Opis: The isoenzyme of human glutathione transferase P1-1 (hGSTP1-1) is involved in multi-drug resistance (MDR) mechanisms in numerous cancer cell lines. In the present study, the inhibition potency of two curcuminoids and eleven monocarbonyl curcumin analogues against hGSTP1-1 was investigated. Demethoxycurcumin (Curcumin II) and three of the monocarbonyl curcumin analogues exhibited the highest inhibitory activity towards hGSTP1-1 with IC50 values ranging between 5.45 1.08 and 37.72 1.02 M. Kinetic inhibition studies of the most potent inhibitors demonstrated that they function as non-competitive/mixed-type inhibitors. These compounds were also evaluated for their toxicity against the prostate cancer cells DU-145. Interestingly, the strongest hGSTP1-1 inhibitor, (DM96), exhibited the highest cytotoxicity with an IC50 of 8.60 1.07 M, while the IC50 values of the rest of the compounds ranged between 44.59–48.52 M. Structural analysis employing molecular docking, molecular dynamics (MD) simulations, and binding-free-energy calculations was performed to study the four most potent curcumin analogues as hGSTP1-1 inhibitors. According to the obtained computational results, DM96 exhibited the lowest binding free energy, which is in agreement with the experimental data. All studied curcumin analogues were found to form hydrophobic interactions with the residue Gln52, as well as hydrogen bonds with the nearby residues Gln65 and Asn67. Additional hydrophobic interactions with the residues Phe9 and Val36 as well as – stacking interaction with Phe9 contributed to the superior inhibitory activity of DM96. The van derWaals component through shape complementarity was found to play the most important role in DM96-inhibitory activity. Overall, our results revealed that the monocarbonyl curcumin derivative DM96 acts as a strong hGSTP1-1 inhibitor, exerts high prostate cancer cell cytotoxicity, and may, therefore, be exploited for the suppression and chemosensitization of cancer cells. This study provides new insights into the development of safe and effective GST-targeted cancer chemosensitizers.
Ključne besede: curcuminoids, curcumin analogues, human glutathione transferase P1-1 (hGSTP1-1), glutathione transferase, enzyme inhibition, multi-drug resistance
Objavljeno v DKUM: 12.03.2024; Ogledov: 288; Prenosov: 13
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4. The role of ascorbate–glutathione system and volatiles emitted by insect-damaged lettuce roots as navigation signals for insect and slug parasitic nematodesŽiga Laznik, Mitja Križman, Jure Zekič, Mihaela Roškarič, Stanislav Trdan, Andreja Urbanek Krajnc, 2023, izvirni znanstveni članek Opis: The effect of wireworm-damaged lettuce roots on the antioxidative defense system (ascorbate–glutathione cycle, photosynthetic pigments) and movement of insect/slug parasitic nematodes towards determined root exudates was studied in a glasshouse experiment. Lettuce seedlings were grown in a substrate soil in the absence/presence of wireworms (Elateridae). The ascorbate– glutathione system and photosynthetic pigments were analyzed by HPLC, while volatile organic compounds (VOC) emitted by lettuce roots were investigated by GC-MS. Herbivore-induced root compounds, namely 2,4-nonadienal, glutathione, and ascorbic acid, were selected for a chemotaxis assay with nematodes Steinernema feltiae, S. carpocapsae, Heterorhabditis bacteriophora, Phasmarhabditis papillosa, and Oscheius myriophilus. Root pests had a negative effect on the content of photosynthetic pigments in the leaves of infested plants, indicating that they reacted to the presence of reactive oxygen species (ROS). Using lettuce as a model plant, we recognized the ascorbate–glutathione system as a redox hub in defense response against wireworms and analyzed its role in root-exudate-mediated chemotaxis of nematodes. Infected plants also demonstrated increased levels of volatile 2,4-nonadienal. Entomopathogenic nematodes (EPNs, S. feltiae, S. carpocapsae, and H. bacteriophora) proved to be more mobile than parasitic nematodes O. myriophilus and P. papillosa towards chemotaxis compounds. Among them, 2,4-nonadienal repelled all tested nematodes. Most exudates that are involved in belowground tritrophic interactions remain unknown, but an increasing effort is being made in this field of research. Understanding more of these complex interactions would not only allow a better understanding of the rhizosphere but could also offer ecologically sound alternatives in the pest management of agricultural systems.
Ključne besede: lettuce, wireworms, ascorbate–glutathione system, root volatile organic compounds, entomopathogenic nematodes, slug parasitic nematodes
Objavljeno v DKUM: 15.02.2024; Ogledov: 395; Prenosov: 24
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5. Variations in leaf total protein, phenolic and thiol contents amongst old varieties of mulberry from the Gorizia regionTina Ugulin, Tamas Bakonyi, Rebeka Lucijana Berčič, Andreja Urbanek Krajnc, 2015, izvirni znanstveni članek Opis: Preserving the plant genetic resources of genus Morus is insuffcient but undoubtedly vital for conservation of the world’s germplasm for our successors. This research was focused on old mulberry varieties from the Gorizia region in Slovenia which were assessed for their contents on crucial metabolites (proteins, phenolics and thiols) in leaves regarding their antioxidant and nutraceutical potentials. Total proteins were measured spectrophotometrically by following the procedure of Bradford, the total phenolic contents were determined using the Folin-Ciocalteu method and thiols were established with monobromobimane fluorescent dye. The presented metabolite screening showed that some of the evaluated genotypes had higher concentrations of glutathione and were superior in contents of proteins and phenolics when compared to the results of other authors and could be propagated as highly recommendable feed for silkworms, and other animals.
Ključne besede: feeds, glutathione, Morus, phenols, proteins
Objavljeno v DKUM: 14.11.2017; Ogledov: 1822; Prenosov: 547
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6. Antioxidant defences of Norway spruce bark against bark beetles and its associated blue-stain fungusMateja Felicijan, Metka Novak, Nada Kraševec, Andreja Urbanek Krajnc, 2015, izvirni znanstveni članek Opis: Bark beetles and their fungal associates are integral parts of forest ecosystems, the European spruce bark beetle (Ips typographus Linnaeus, 1758) and the associated pathogenic blue stain fungus Ceratocystis polonica (SIEM.) C. MOREAU, are the most devastating pests regarding Norway spruce [Picea abies (L.) H. KARST.]. Bark beetles commonly inhabit weakened and felled trees as well as vital trees. They cause physiological disorders in trees by destroying a phloem and cambium or interrupt the transpiration -ow in the xylem. Conifers have a wide range of effective defence mechanisms that are based on the inner bark anatomy and physiological state of the tree. The basic function of bark defences is to protect the nutrient-and energy-rich phloem, the vital meristematic region of the vascular cambium, and the transpiration -ow in the sapwood. The main area of defence mechanisms is secondary phloem, which is physically and chemically protected by polyphenolic parenchyma (PP) cells, sclerenchyma, calcium oxalate crystals and resin ducts. Conifer trunk pest resistance includes constitutive, inducible defences and acquired resistance. Both constitutive and inducible defences may deter beetle invasion, impede fungal growth and close entrance wounds. During a successful attack, systemic acquired resistance (SAR) becomes effective and represents a third defence strategy. It gradually develops throughout the plant and provides a systemic change within the whole tree’s metabolism, which is maintained over a longer period of time. The broad range of defence mechanisms that contribute to the activation and utilisation of SAR, includes antioxidants and antioxidant enzymes, which are generally linked to the actions of reactive oxygen species (ROS). The presented review discusses the current knowledge on the antioxidant defence strategies of spruce inner bark against the bark beetle (Ips typographus) and associated blue stain fungus (Ceratocystis polonica).
Ključne besede: antioxidants, ascorbate-glutathione system, blue-stain fungus, Norway spruce, phenolics, systemic acquired resistance
Objavljeno v DKUM: 14.11.2017; Ogledov: 1794; Prenosov: 464
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7. An Insight into the defense mechanisms and the role of glutathione during advanced ZYMV infection in Styrian oil pumpkinAndreja Urbanek Krajnc, Maria Müller, 2006, izvirni znanstveni članek Ključne besede: Cucurbita pepo, Styrian oil pumpkin, Zucchini yellow mosaic virus, reactive oxygen species, systemic acquired resistance, glutathione, L-2-oxothiazolidine-4-carboxylic acid, salicylic acid, somatic embryogenesis, virus tolerance
Objavljeno v DKUM: 10.07.2015; Ogledov: 1487; Prenosov: 44
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