TY - JOUR AU - Kincses, Annamária AU - Szemerédi, Nikoletta AU - Benito‐Lama, Miguel AU - Dózsai, Dávid AU - Csonka, Ákos AU - Domínguez‐Álvarez, Enrique AU - Spengler, Gabriella TI - Selenocompounds as Potent Efflux Pump Inhibitors on Gram‐positive Bacteria JF - CHEMMEDCHEM J2 - CHEMMEDCHEM VL - 20 PY - 2025 IS - 2 PG - 11 SN - 1860-7179 DO - 10.1002/cmdc.202400691 UR - https://m2.mtmt.hu/api/publication/35594147 ID - 35594147 N1 - Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis street 6, Szeged, 6725, Hungary Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös street 6, Szeged, 6720, Hungary Instituto de Química Orgánica General (IQOG), Consejo Superior de Organizaciones Científicas (CSIC), Juan de la Cierva 3, Madrid, 28006, Spain Department of Traumatology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis street 6, Szeged, 6725, Hungary Export Date: 14 January 2025 CODEN: CHEMG Correspondence Address: Spengler, G.; Department of Medical Microbiology, Semmelweis street 6, Hungary; email: spengler.gabriella@med.u-szeged.hu Correspondence Address: Domínguez-Álvarez, E.; Instituto de Química Orgánica General (IQOG), Juan de la Cierva 3, Spain; email: e.dominguez-alvarez@iqog.csic.es AB - In recent years, selenocompounds have gained increasing attention as potential anticancer and antibacterial agents. Several selenoderivatives have been confirmed to act as MDR efflux pump inhibitors, based on their in vitro results against the bacterial AcrAB‐TolC system and the cancer MDR efflux pump P‐glycoprotein. Efflux pumps can contribute directly or indirectly to the virulence of bacteria, as they can reduce the intracellular concentration of antibacterial substances by expelling them out of the cell. The present work aims to study the antibacterial and efflux pump inhibiting properties of four families of selenoesters, namely aspirin‐selenoesters, phenone‐selenoesters, hydroxy‐selenoesters, and benzyl‐selenoesters. The real‐time ethidium bromide accumulation assay confirmed that these derivatives inhibited the efflux systems of methicillin‐resistant Staphylococcus aureus (MRSA) without exerting any antibacterial effect. The relative expression of efflux pump gene of NorA transporter was also monitored in the presence of the most potent derivatives on reference S. aureus , finding that these derivatives could change the expression of the tested efflux pump gene. Regarding the anti‐biofilm activity, aspirin‐selenoesters, benzyl‐selenoesters, and hydroxy‐selenoesters could efficiently inhibit the biofilm production of the MRSA strain. It can be concluded that selenocompounds could act as efflux pump inhibitors, thus reducing the virulence of biofilm‐producing bacteria. LA - English DB - MTMT ER - TY - JOUR AU - Gátszegi, Gerda T. AU - Petrasheuskaya, Tatsiana AU - May, Nóra Veronika AU - Hajdu, Bálint AU - Spengler, Gabriella AU - Bacher, Felix AU - Shova, Sergiu AU - Arion, Vladimir B. AU - Enyedy, Éva Anna TI - Solution equilibrium and redox properties of metal complexes with 2-formylpyridine guanylhydrazone derivatives: Effect of morpholine and piperazine substitutions JF - JOURNAL OF INORGANIC BIOCHEMISTRY J2 - J INORG BIOCHEM VL - 264 PY - 2025 PG - 14 SN - 0162-0134 DO - 10.1016/j.jinorgbio.2024.112812 UR - https://m2.mtmt.hu/api/publication/35631990 ID - 35631990 N1 - Funding Agency and Grant Number: Distinguished Guest Scientist Fellowship Program of the Hungarian Academy of Sciences; University Research Fellowship Programme of the Ministry of Culture and Innovation [EKOP-24-2-EKOP-444]; OeAD Ernst Mach grant; Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund [TKP2021-EGA-32, TKP2021-EGA]; [MPC-2021-00073] Funding text: V.B.A. was supported by the Distinguished Guest Scientist Fellowship Program of the Hungarian Academy of Sciences, and EKOP-24-2-EKOP-444 University Research Fellowship Programme of the Ministry of Culture and Innovation (G.T.G.) and OeAD Ernst Mach grant MPC-2021-00073 are also acknowledged (T.V.P.) . Project no TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. We thank Dr. Tim Gruene and the team of the Centre for X-ray Structural Analysis (Faculty of Chemistry, University of Vienna) for X-ray diffraction measurements. AB - Schiff bases derived from aminoguanidine are extensively investigated for their structural versatility. The tridentate 2-formylpyridine guanylhydrazones act as analogues of 2-formyl or 2-acetylpyridine thiosemicarbazones, where the thioamide unit is replaced by the guanidyl group. Six derivatives of 2-formylpyridine guanylhydrazone were synthesized and their proton dissociation and complex formation processes with Cu(II), Fe(II) and Fe(III) ions were studied using pH-potentiometry, UV–visible, NMR and electron paramagnetic resonance spectroscopic methods. The ligands have substituents such as amine, morpholine, N-methyl-piperazine at different positions of the pyridine ring. The influence of the different structural elements on the solution chemical properties and cytotoxicity has been disclosed. The solid state structure of four ligands was determined by X-ray crystallography. The ligands bind to Cu(II) in a tridentate fashion via an (N,N,N) donor set, forming mono-ligand complexes. However, for ligands with heterocyclic morpholine and piperazine nitrogen atoms in coordination position a tetradentate binding was observed. Despite the additional coordinating donor atom, the stability of these Cu(II) complexes showed little or no increase. The Cu(II), Fe(II) and Fe(III) complexes of the studied 2-formylpyridine guanylhydrazones exhibited significantly lower stability compared to their corresponding 2-formyl or 2-acetylpyridine thiosemicarbazone analogues. The ligands underwent slow partial hydrolysis (and oxidation) in the presence of Cu(II) ions, leading to the formation of new ligands through the reorganization of structural components around the metal ion. Additionally, the studied Cu(II) complexes demonstrated a great propensity for reduction by glutathione. All these features contributed to the finding that these 2-formylpyridine guanylhydrazones and their Cu(II) complexes did not display measurable cytotoxic activity. LA - English DB - MTMT ER - TY - JOUR AU - Rózsa, Árpád AU - Orosz, László AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Kecskeméti, Gábor AU - Vágó, Otília AU - Sárvári, Károly Péter AU - Szabó, Diána AU - Szabó, Zoltán AU - Burián, Katalin AU - Virók, Dezső TI - Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL Escherichia coli JF - ANTIBIOTICS J2 - ANTIBIOTICS-BASEL VL - 14 PY - 2025 IS - 1 PG - 13 SN - 2079-6382 DO - 10.3390/antibiotics14010076 UR - https://m2.mtmt.hu/api/publication/35693515 ID - 35693515 N1 - Funding: K.B. and D.P.V. were supported by the Albert Szent-Györgyi Grant of the University of Szeged. AB - Background/Objectives: Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as Escherichia coli. In this study, we explored the effects of a bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive E. coli isolate. Methods: We used next generation sequencing, proteomics and phenotypic screens to investigate the effect of bacteriophage infections on E. coli metabolism and resistance phenotypes. Results: The bacteriophage infection led to notable alterations in colony morphology, indicating profound changes in bacterial metabolism. Proteomic analysis revealed significant shifts in protein expression, with 65 proteins upregulated and 246 downregulated post-infection. The downregulated proteins were involved in various metabolic pathways, including nucleic acid, protein and lipid metabolism, and iron acquisition. Bacteriophage treatment also led to increased bacterial membrane permeability. Altogether, these alterations in bacterial metabolism and membrane permeability may lead to a general reduction in antibiotic resistance. Indeed, the bacteriophage-infected E. coli exhibited increased sensitivity to various classes of antibiotics, including beta-lactams, fluoroquinolones, trimethoprim-sulfamethoxazole, and aminoglycosides. Conclusions: Our findings highlight the potential of bacteriophage therapy as an adjunct to existing antibiotics, enhancing their efficacy against resistant strains. LA - English DB - MTMT ER - TY - JOUR AU - Pivarcsik, Tamás AU - Kovács, Ferenc AU - Spengler, Gabriella AU - Nové, Márta AU - Keppler, Bernhard K. AU - Kandioller, Wolfgang AU - Nagyné Frank, Éva AU - Enyedy, Éva Anna TI - Anticancer organometallic half-sandwich complexes of estrone-derived (N,N) donor ligands with enhanced aqueous solubility JF - JOURNAL OF INORGANIC BIOCHEMISTRY J2 - J INORG BIOCHEM VL - 267 PY - 2025 PG - 13 SN - 0162-0134 DO - 10.1016/j.jinorgbio.2025.112858 UR - https://m2.mtmt.hu/api/publication/35777618 ID - 35777618 LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Dóra AU - Szemerédi, Nikoletta AU - Gubó, Dorka AU - Spengler, Gabriella AU - Szatmári, István TI - Synthesis, transformations and biological evaluation of 5‑chloro-8-hydroxyquinoline hybrids JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 209 PY - 2025 PG - 9 SN - 0928-0987 DO - 10.1016/j.ejps.2025.107084 UR - https://m2.mtmt.hu/api/publication/36082707 ID - 36082707 LA - English DB - MTMT ER - TY - JOUR AU - Ashimbayeva, Meruyert AU - Szakonyi, Zsolt AU - Adekenov, Sergazy M. AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Le Minh, Tam TI - Synthesis and Antiproliferative Effects of Grossheimin-Derived Aminoanalogues JF - BIOMOLECULES J2 - BIOMOLECULES VL - 15 PY - 2025 IS - 4 PG - 12 SN - 2218-273X DO - 10.3390/biom15040578 UR - https://m2.mtmt.hu/api/publication/36093276 ID - 36093276 AB - Grossheimin, a guaiane-type sesquiterpene lactone, displayed a diverse range of biological activities, including anticancer, anti-inflammatory and antimicrobial effects. Various amino analogues of grossheimin were prepared through a Michael addition at its highly active α-methylene-γ-lactone motif. On the other hand, grossheimin was reduced to diol, which was then subjected to nucleophilic addition or acetylation to introduce heteroatoms associated with oxygen, sulfur or nitrogen functionalities. All of the synthesised Michael and acetylated adducts were evaluated for their in vitro cytotoxic action on human colon adenocarcinoma lines, including Colo205 and Colo320. The bioassay results indicated that the acetylated adducts displayed a potent cytotoxic effect compared to grossheimin, the parent molecule. A docking study was also performed to exploit the observed results. LA - English DB - MTMT ER - TY - JOUR AU - Moustafa, Reem AU - Remete, Attila Márió AU - Szakonyi, Zsolt AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Le Minh, Tam TI - Synthesis and Antimicrobial Evaluation of (+)-Neoisopulegol-Based Amino and Thiol Adducts JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 26 PY - 2025 IS - 10 PG - 23 SN - 1661-6596 DO - 10.3390/ijms26104791 UR - https://m2.mtmt.hu/api/publication/36150681 ID - 36150681 AB - A library of neoisopulegol-based amino and thiol adducts was developed from (+)-neoisopulegol, derived from commercially available (−)-isopulegol. Michael addition of different nucleophiles towards its highly active α,β-unsaturated γ-lactone motif was accomplished, resulting in diverse amino and thiol analogs in stereoselective reactions. Then, the lactone ring was opened, with NH3 and benzylamine furnishing primary amide and N-benzyl-substituted amide derivatives, respectively. The in vitro antimicrobial effect of prepared compounds was also explored. The results revealed that naphthylmethyl-substituted β-aminolactone, the most promising compound, displayed selective inhibition for the Gram-positive bacteria S. aureus with an MIC (minimum inhibitory concentration) value of 12.5 μM. A docking study was performed to interpret the obtained results. LA - English DB - MTMT ER - TY - JOUR AU - Sousa, Maria Ligia AU - Ferreira, Leonor AU - Ferreira, Dora AU - Forero, Abel M. AU - Castelo-Branco, Raquel AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Rodriguez, Jaime AU - Jimenez, Carlos AU - Leao, Pedro N. AU - Vasconcelos, Vitor AU - Reis, Mariana Alves TI - Decoding Lusichelins A-E: An In-Depth Look at the Metallophores of Lusitaniella coriacea LEGE 07167-Structure, Production, and Functionality JF - JOURNAL OF NATURAL PRODUCTS J2 - J NAT PROD PY - 2025 PG - 15 SN - 0163-3864 DO - 10.1021/acs.jnatprod.5c00204 UR - https://m2.mtmt.hu/api/publication/36174627 ID - 36174627 N1 - Funding Agency and Grant Number: Portuguese Foundation for Science and Technology (FCT) [C644915664-00000026]; PRR, The Portuguese Republic; European Union; Spanish State Agency for Research [ED431C 2022/39]; FEDER Program from the European Union; Xunta de Galicia (Spain); Hungarian Academy of Sciences [SFRH/BD/136367/2018]; BYT CIIMAR program for the BYTplus scholarship; MCIN/AEI [PID2021-122732OB-C22]; [UIDB/04423/2020]; [UIDP/04423/2020]; [952374]; [BO/00158/22/5] Funding text: This research was supported by the Portuguese Foundation for Science and Technology (FCT) within the scope of UIDB/04423/2020 and UIDP/04423/2020 and the WP9-Portuguese Blue Biobank under the Blue Economy Pact project no. C644915664-00000026 cofunded by PRR, The Portuguese Republic, and the European Union. This project has also received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 952374. The work was also supported by grant PID2021-122732OB-C22 from MCIN/AEI/10.13039/501100011033/ FEDER "A way to make Europe" (AEI, Spanish State Agency for Research and FEDER Program from the European Union) and grant ED431C 2022/39 from Xunta de Galicia (Spain). G.S. was supported by the Janos Bolyai Research Scholarship (BO/00158/22/5) of the Hungarian Academy of Sciences. L.F. acknowledges the FCT grant 2022.11979.BD. R.C.B. acknowledges the FCT grant SFRH/BD/136367/2018. D.F. thanks the BYT CIIMAR program for the BYTplus scholarship. The authors thank the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) at CIIMAR (https://lege.ciimar.up.pt/) for their support. AB - Essential trace metals are vital for cellular processes, such as respiration, DNA replication, and photosynthesis. Cyanobacteria must tightly regulate metal homeostasis to prevent deficiency or toxicity, yet their metallophores remain overlooked. Here, we report lusichelins A-E (1-5), new metallophores isolated from the marine cyanobacterium Lusitaniella coriacea LEGE 07167. Their structures and configurational assignments were determined by using NMR, mass spectrometry, TD-DFT calculations, and retrobiosynthetic insights. Lusichelins feature a unique structural arrangement with thiazoline/thiazole rings connected via a vinyl group, an aliphatic carbon chain, or directly enabling the potential for metal coordination. Genomic analysis identified a hybrid PKS/NRPS biosynthetic gene cluster consistent with the lusichelin structure, bearing traits characteristic of metallophore biosynthesis. Functionally, lusichelins act as metallophores capable of chelating both iron and copper. Lusichelin C (3) consistently bound iron under both metal-rich and metal-limited culture conditions, while copper complexation was only observed under elevated copper levels. At physiologically relevant pH values, no significant metal-binding preference was detected. Moreover, compound production was maximized under metal-rich conditions and in response to copper limitation. Lusichelin B (2) exhibited cytotoxicity against colon carcinoma cells while reversing multidrug resistance via ABCB1 efflux pump modulation. These findings expand our understanding of cyanobacterial metallophores in microbial metal homeostasis and highlight their biological potential. LA - English DB - MTMT ER - TY - JOUR AU - Kincses, Annamária AU - Abu Ghazal, Tasneem AU - Veres, Katalin AU - Spengler, Gabriella AU - Hohmann, Judit TI - Phenolic compounds from Origanum majorana with biofilm-inhibitory activity against methicillin-resistant Staphylococcus aureus and Escherichia coli strains JF - PHARMACEUTICAL BIOLOGY J2 - PHARM BIOL VL - 63 PY - 2025 IS - 1 SP - 402 EP - 410 PG - 9 SN - 1388-0209 DO - 10.1080/13880209.2025.2511805 UR - https://m2.mtmt.hu/api/publication/36175758 ID - 36175758 LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Dóra AU - Szemerédi, Nikoletta AU - Spengler, Gabriella AU - Szatmári, István TI - Synthesis and Transformations of Bioactive Scaffolds via Modified Mannich and aza ‐Friedel–Crafts Reactions JF - CHEMICAL RECORD J2 - CHEM REC PY - 2025 PG - 31 SN - 1527-8999 DO - 10.1002/tcr.202500077 UR - https://m2.mtmt.hu/api/publication/36186317 ID - 36186317 AB - This account summarizes the synthesis of bifunctional glycine‐type precursors substituted with 2‐ and 1‐naphthol. The stabilization of precursors via partially aromatic ortho ‐quinone methide intermediate is tested with different cyclic imines in [4 + 2] cycloaddition. 8‐Hydroxyquinoline is a biologically active moiety considered as a formal 1‐naphthol analog, hence the behavior of the scaffold in Mannich reaction is examined. The possibility of transformation of glycine derivatives substituted with 2‐ and 1‐naphthol as well as the formed Mannich base consisting 5‐chloro‐8‐hydroxyquinoline skeleton to give diarylmethane derivatives with indole and 7‐azaindole are studied. A series of cyclic amines coupled with indole and azaindole derivatives has been systematically designed and their biological examination is achieved. To have a preliminary overview about the structure–activity relationship, the antibacterial and anticancer activity of synthesized compounds by preliminary biological screening systems is tested. LA - English DB - MTMT ER -