@article{MTMT:35594147, title = {Selenocompounds as Potent Efflux Pump Inhibitors on Gram‐positive Bacteria}, url = {https://m2.mtmt.hu/api/publication/35594147}, author = {Kincses, Annamária and Szemerédi, Nikoletta and Benito‐Lama, Miguel and Dózsai, Dávid and Csonka, Ákos and Domínguez‐Álvarez, Enrique and Spengler, Gabriella}, doi = {10.1002/cmdc.202400691}, journal-iso = {CHEMMEDCHEM}, journal = {CHEMMEDCHEM}, volume = {20}, unique-id = {35594147}, issn = {1860-7179}, abstract = {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.}, keywords = {Selenium; multidrug resistance; biological activity; efflux pump; Biofilm}, year = {2025}, eissn = {1860-7187}, orcid-numbers = {Kincses, Annamária/0000-0002-1591-1419; Spengler, Gabriella/0000-0001-8085-0950} } @article{MTMT:35631990, title = {Solution equilibrium and redox properties of metal complexes with 2-formylpyridine guanylhydrazone derivatives: Effect of morpholine and piperazine substitutions}, url = {https://m2.mtmt.hu/api/publication/35631990}, author = {Gátszegi, Gerda T. and Petrasheuskaya, Tatsiana and May, Nóra Veronika and Hajdu, Bálint and Spengler, Gabriella and Bacher, Felix and Shova, Sergiu and Arion, Vladimir B. and Enyedy, Éva Anna}, doi = {10.1016/j.jinorgbio.2024.112812}, journal-iso = {J INORG BIOCHEM}, journal = {JOURNAL OF INORGANIC BIOCHEMISTRY}, volume = {264}, unique-id = {35631990}, issn = {0162-0134}, abstract = {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.}, year = {2025}, eissn = {1873-3344}, orcid-numbers = {May, Nóra Veronika/0000-0003-4770-4681; Spengler, Gabriella/0000-0001-8085-0950; Enyedy, Éva Anna/0000-0002-8058-8128} } @article{MTMT:35693515, title = {Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL Escherichia coli}, url = {https://m2.mtmt.hu/api/publication/35693515}, author = {Rózsa, Árpád and Orosz, László and Szemerédi, Nikoletta and Spengler, Gabriella and Kecskeméti, Gábor and Vágó, Otília and Sárvári, Károly Péter and Szabó, Diána and Szabó, Zoltán and Burián, Katalin and Virók, Dezső}, doi = {10.3390/antibiotics14010076}, journal-iso = {ANTIBIOTICS-BASEL}, journal = {ANTIBIOTICS}, volume = {14}, unique-id = {35693515}, issn = {2079-6382}, abstract = {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.}, year = {2025}, eissn = {2079-6382}, orcid-numbers = {Spengler, Gabriella/0000-0001-8085-0950; Kecskeméti, Gábor/0000-0002-5584-6869; Sárvári, Károly Péter/0000-0001-9926-0918; Szabó, Zoltán/0000-0001-8278-8038; Burián, Katalin/0000-0003-1300-2374} } @article{MTMT:35777618, title = {Anticancer organometallic half-sandwich complexes of estrone-derived (N,N) donor ligands with enhanced aqueous solubility}, url = {https://m2.mtmt.hu/api/publication/35777618}, author = {Pivarcsik, Tamás and Kovács, Ferenc and Spengler, Gabriella and Nové, Márta and Keppler, Bernhard K. and Kandioller, Wolfgang and Nagyné Frank, Éva and Enyedy, Éva Anna}, doi = {10.1016/j.jinorgbio.2025.112858}, journal-iso = {J INORG BIOCHEM}, journal = {JOURNAL OF INORGANIC BIOCHEMISTRY}, volume = {267}, unique-id = {35777618}, issn = {0162-0134}, year = {2025}, eissn = {1873-3344}, orcid-numbers = {Spengler, Gabriella/0000-0001-8085-0950; Nagyné Frank, Éva/0000-0002-1332-0551; Enyedy, Éva Anna/0000-0002-8058-8128} } @article{MTMT:36082707, title = {Synthesis, transformations and biological evaluation of 5‑chloro-8-hydroxyquinoline hybrids}, url = {https://m2.mtmt.hu/api/publication/36082707}, author = {Hegedűs, Dóra and Szemerédi, Nikoletta and Gubó, Dorka and Spengler, Gabriella and Szatmári, István}, doi = {10.1016/j.ejps.2025.107084}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {209}, unique-id = {36082707}, issn = {0928-0987}, year = {2025}, eissn = {1879-0720}, orcid-numbers = {Spengler, Gabriella/0000-0001-8085-0950; Szatmári, István/0000-0002-8571-5229} } @article{MTMT:36093276, title = {Synthesis and Antiproliferative Effects of Grossheimin-Derived Aminoanalogues}, url = {https://m2.mtmt.hu/api/publication/36093276}, author = {Ashimbayeva, Meruyert and Szakonyi, Zsolt and Adekenov, Sergazy M. and Szemerédi, Nikoletta and Spengler, Gabriella and Le Minh, Tam}, doi = {10.3390/biom15040578}, journal-iso = {BIOMOLECULES}, journal = {BIOMOLECULES}, volume = {15}, unique-id = {36093276}, issn = {2218-273X}, abstract = {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.}, year = {2025}, eissn = {2218-273X}, orcid-numbers = {Ashimbayeva, Meruyert/0000-0001-6412-3892; Szakonyi, Zsolt/0000-0003-2432-8409; Adekenov, Sergazy M./0000-0001-7588-6174; Spengler, Gabriella/0000-0001-8085-0950; Le Minh, Tam/0000-0002-8296-887X} } @article{MTMT:36150681, title = {Synthesis and Antimicrobial Evaluation of (+)-Neoisopulegol-Based Amino and Thiol Adducts}, url = {https://m2.mtmt.hu/api/publication/36150681}, author = {Moustafa, Reem and Remete, Attila Márió and Szakonyi, Zsolt and Szemerédi, Nikoletta and Spengler, Gabriella and Le Minh, Tam}, doi = {10.3390/ijms26104791}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {26}, unique-id = {36150681}, issn = {1661-6596}, abstract = {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.}, year = {2025}, eissn = {1422-0067}, orcid-numbers = {Remete, Attila Márió/0000-0001-6388-0197; Szakonyi, Zsolt/0000-0003-2432-8409; Spengler, Gabriella/0000-0001-8085-0950; Le Minh, Tam/0000-0002-8296-887X} } @article{MTMT:36174627, title = {Decoding Lusichelins A-E: An In-Depth Look at the Metallophores of Lusitaniella coriacea LEGE 07167-Structure, Production, and Functionality}, url = {https://m2.mtmt.hu/api/publication/36174627}, author = {Sousa, Maria Ligia and Ferreira, Leonor and Ferreira, Dora and Forero, Abel M. and Castelo-Branco, Raquel and Szemerédi, Nikoletta and Spengler, Gabriella and Rodriguez, Jaime and Jimenez, Carlos and Leao, Pedro N. and Vasconcelos, Vitor and Reis, Mariana Alves}, doi = {10.1021/acs.jnatprod.5c00204}, journal-iso = {J NAT PROD}, journal = {JOURNAL OF NATURAL PRODUCTS}, volume = {88}, unique-id = {36174627}, issn = {0163-3864}, abstract = {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.}, keywords = {CONFIGURATION; biosynthesis; CYANOBACTERIA; SIDEROPHORE; Chemistry, Medicinal; Plant Sciences; POLYCHLORINATED LEUCINE DERIVATIVES}, year = {2025}, eissn = {1520-6025}, pages = {1319-1333}, orcid-numbers = {Spengler, Gabriella/0000-0001-8085-0950} } @article{MTMT:36175758, title = {Phenolic compounds from Origanum majorana with biofilm-inhibitory activity against methicillin-resistant Staphylococcus aureus and Escherichia coli strains}, url = {https://m2.mtmt.hu/api/publication/36175758}, author = {Kincses, Annamária and Abu Ghazal, Tasneem and Veres, Katalin and Spengler, Gabriella and Hohmann, Judit}, doi = {10.1080/13880209.2025.2511805}, journal-iso = {PHARM BIOL}, journal = {PHARMACEUTICAL BIOLOGY}, volume = {63}, unique-id = {36175758}, issn = {1388-0209}, year = {2025}, eissn = {1744-5116}, pages = {402-410}, orcid-numbers = {Kincses, Annamária/0000-0002-1591-1419; Abu Ghazal, Tasneem/0000-0003-1574-5948; Veres, Katalin/0000-0001-7108-3622; Spengler, Gabriella/0000-0001-8085-0950; Hohmann, Judit/0000-0002-2887-6392} } @article{MTMT:36186317, title = {Synthesis and Transformations of Bioactive Scaffolds via Modified Mannich and aza ‐Friedel–Crafts Reactions}, url = {https://m2.mtmt.hu/api/publication/36186317}, author = {Hegedűs, Dóra and Szemerédi, Nikoletta and Spengler, Gabriella and Szatmári, István}, doi = {10.1002/tcr.202500077}, journal-iso = {CHEM REC}, journal = {CHEMICAL RECORD}, unique-id = {36186317}, issn = {1527-8999}, abstract = {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.}, year = {2025}, eissn = {1528-0691}, orcid-numbers = {Spengler, Gabriella/0000-0001-8085-0950; Szatmári, István/0000-0002-8571-5229} }