@article{MTMT:34861986, title = {Diagnosis of Melanoma with 61 Cu-Labeled PET Tracer}, url = {https://m2.mtmt.hu/api/publication/34861986}, author = {Bunda, Szilvia and Kálmán-Szabó, Ibolya and Lihi, Norbert and Képes, Zita and Szikra, Dezső and Péliné Szabó, Judit and Timári, István and Szücs, Dániel and May, Nóra Veronika and Papp, Gábor Csaba and Trencsényi, György and Kálmán, Ferenc Krisztián}, doi = {10.1021/acs.jmedchem.4c00479}, journal-iso = {J MED CHEM}, journal = {JOURNAL OF MEDICINAL CHEMISTRY}, unique-id = {34861986}, issn = {0022-2623}, year = {2024}, eissn = {1520-4804}, orcid-numbers = {Lihi, Norbert/0000-0003-2986-2395; Képes, Zita/0000-0003-2889-8521; May, Nóra Veronika/0000-0003-4770-4681; Trencsényi, György/0000-0001-6456-6212} } @article{MTMT:34846781, title = {Competing Domino Knoevenagel-Cyclization Sequences with N -Arylcinnamylamines}, url = {https://m2.mtmt.hu/api/publication/34846781}, author = {Kajtár, Mihály and Király, Sándor Balázs and Bényei, Attila and Kiss, Attila and Kónya-Ábrahám, Anita and Zhang, Ning and Horváth, Lilla and Bősze, Szilvia and Li, Dehai and Kotschy, András and Paczal, Attila and Kurtán, Tibor}, doi = {10.1021/acs.joc.4c00299}, journal-iso = {J ORG CHEM}, journal = {JOURNAL OF ORGANIC CHEMISTRY}, unique-id = {34846781}, issn = {0022-3263}, abstract = {Domino Knoevenagel-cyclization reactions of Narylcinnamylamines were carried out with active methylene reagents, which took place with five competing cyclization mechanisms: intramolecular hetero Diels-Alder reaction, stepwise polar [2 + 2] cycloaddition, styryl or aza-Diels-Alder reactions followed by rearomatization, and [1,5]-hydride shift-6-endo cyclization. In the stepwise aza-Diels-Alder reaction, the Nvinylpyridinium moiety acted as an azadiene, producing a condensed heterocycle with tetrahydroquinolizinium and tetrahydroquiniline subunits. Antiproliferative activity with low micromolar IC50 values was identified for some of the novel scaffolds.}, year = {2024}, eissn = {1520-6904}, orcid-numbers = {Bényei, Attila/0000-0002-0617-6264; Kiss, Attila/0000-0003-3601-5143; Bősze, Szilvia/0000-0001-9555-699X; Li, Dehai/0000-0002-7191-2002; Kotschy, András/0000-0002-7675-3864} } @article{MTMT:34813914, title = {Synthesis, in silico and kinetics evaluation of N-(beta-D-glucopyranosyl)-2-arylimidazole-4(5)-carboxamides and N-(beta-D-glucopyranosyl)-4(5)-arylimidazole-2-carboxamides as glycogen phosphorylase inhibitors}, url = {https://m2.mtmt.hu/api/publication/34813914}, author = {Homolya, Levente and Mathomes, Rachel T. and Fodor-Varga, Luca Anna and Docsa, Tibor and Juhász, László and Hayes, Joseph M. and Somsák, László}, doi = {10.3390/ijms25094591}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34813914}, issn = {1661-6596}, abstract = {Recently studied N-(β-D-glucopyranosyl)-3-aryl-1,2,4-triazole-5-carboxamides have proven to be low micromolar inhibitors of glycogen phosphorylase (GP), a validated target for the treatment of type 2 diabetes mellitus. Since in other settings, the bioisosteric replacement of the 1,2,4-triazole moiety with imidazole resulted in significantly more efficient GP inhibitors, in silico calculations using Glide molecular docking along with unbound state DFT calculations were performed on N-(β-Dglucopyranosyl)-arylimidazole-carboxamides, revealing their potential for strong GP inhibition. The syntheses of the target compounds involved the formation of an amide bond between per-O-acetylated β-D-glucopyranosylamine and the corresponding arylimidazole-carboxylic acids. Kinetics experiments on rabbit muscle GPb revealed low micromolar inhibitors, with the best inhibition constants (Kis) of ~3–4 µM obtained for 1- and 2-naphthyl-substituted N-(β-D-glucopyranosyl)-imidazolecarboxamides, 2b–c. The predicted protein–ligand interactions responsible for the observed potencies are discussed and will facilitate the structure-based design of other inhibitors targeting this important therapeutic target. Meanwhile, the importance of the careful consideration of ligand tautomeric states in binding calculations is highlighted, with the usefulness of DFT calculations in this regard proposed.}, keywords = {Glycogen phosphorylase inhibitor; Tautomers; type 2 diabetes; glucose analogues}, year = {2024}, eissn = {1422-0067}, pages = {1-21}, orcid-numbers = {Juhász, László/0000-0002-7462-7944; Somsák, László/0000-0002-9103-9845} } @article{MTMT:34804043, title = {Colletodiol derivatives of the endophytic fungus Trichocladium sp.}, url = {https://m2.mtmt.hu/api/publication/34804043}, author = {Simons, Viktor E. and Mándi, Attila and Frank, Marian and van Geelen, Lasse and Tran-Cong, Nam and Albrecht, Dorothea and Coort, Annika and Gebhard, Christina and Kurtán, Tibor and Kalscheuer, Rainer}, doi = {10.1016/j.fitote.2024.105914}, journal-iso = {FITOTERAPIA}, journal = {FITOTERAPIA}, volume = {175}, unique-id = {34804043}, issn = {0367-326X}, abstract = {The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied the OSMAC-approach to the endophytic fungus Trichocladium sp. by supplementation of the cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic acid (3), colletolactone (4) and colletolic acid (5), together with five previously described ones (6–10). The structures were elucidated via comprehensive spectroscopic measurements, and the absolute configurations of compound 1 was elucidated by using TDDFT-ECD calculations. For formation of compounds 3–5, a pathway based on colletodiol biosynthesis is proposed. Compound 6 exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 0.78 μM as well as a strong cytotoxic effect against the human monocytic cell line THP1 with an IC50 of 0.7 μM. Compound 8 showed moderate antibacterial activity against Mycobacterium tuberculosis with a MIC of 25 μM and a weak cytotoxic effect against THP1 cells with an IC50 of 42 μM.}, keywords = {CYTOTOXICITY; biosynthesis; antibacterial activity; OSMAC; Trichocladium sp.; Dihydronaphthalenone; Macrocarpon; Colletodiol precursors}, year = {2024}, eissn = {1873-6971} } @article{MTMT:34795040, title = {Omnipolyphilins A and B: Chlorinated Cyclotetrapeptides and Naphtho-α-pyranones from the Plant Nematode-Derived Fungus Polyphilus sieberi}, url = {https://m2.mtmt.hu/api/publication/34795040}, author = {Wennrich, Jan-Peer and Ebada, Sherif S. and Sepanian, Ellen and Holzenkamp, Caren and Khalid, Syeda J. and Schrey, Hedda and Maier, Wolfgang and Mándi, Attila and Kurtán, Tibor and Ashrafi, Samad and Stadler, Marc}, doi = {10.1021/acs.jafc.4c00572}, journal-iso = {J AGR FOOD CHEM}, journal = {JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, volume = {72}, unique-id = {34795040}, issn = {0021-8561}, abstract = {Chemical exploration for two isolates of the recently described ascomycete species Polyphilus sieberi, derived from the eggs of the plant parasitic nematode Heterodera filipjevi, afforded the identification of many compounds that belong to various metabolite families: two previously undescribed chlorinated cyclotetrapeptides, omnipolyphilins A (1) and B (2), one new pyranonaphthoquinone, ventiloquinone P (3), a 6,6′-binaphto-α-pyranone dimer, talaroderxine D (4) in addition to nine known metabolites (5-13) were isolated from this biocontrol candidate. All isolated compounds were characterized by comprehensive 1D, 2D NMR, and HR-ESI-MS analyses. The absolute configurations of the cyclotetrapeptides were determined by a combination of advanced Marfey’s method, ROE correlation aided by conformational analysis, and TDDFT-ECD calculations, while ECD calculations, Mosher’s method, and experimental ECD spectra were used for ventiloquinone P (3) and talaroderxine D (4). Among the isolated compounds, talaroderxine D (4) showed potent antimicrobial activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 2.1 and 8.3 μg mL-1, respectively. Additionally, promising inhibitory effects on talaroderxine D (4) against the formation of S. aureus biofilms were observed up to a concentration of 0.25 μg mL-1. Moreover, ophiocordylongiiside A (10) showed activity against the free-living nematode Caenorhabditis elegans.}, keywords = {Antimicrobial; Helotiales; Nematicidal; naphthopyranones; cyclotetrapeptides}, year = {2024}, eissn = {1520-5118}, pages = {6998-7009} } @article{MTMT:34743720, title = {Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity}, url = {https://m2.mtmt.hu/api/publication/34743720}, author = {Dibello, Estefanía and Oddone, Natalia and Franco, Jaime and Tóthné Illyés, Tünde Zita and Medeiros, Andrea and Kiss, Attila and Hőgye, Fanni and E Kövér, Katalin and Szilágyi, László and Comini, Marcelo A.}, doi = {10.1016/j.ijpddr.2024.100529}, journal-iso = {INT J PARASITOL-DRUG}, journal = {INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE}, volume = {24}, unique-id = {34743720}, issn = {2211-3207}, abstract = {Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 μM) but poorly selective (selectivity index <10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC50 against bloodstream Trypanosoma brucei in the sub-μM range (IC50 0.35–0.77 μM) and four of them showed an improved selectivity (selectivity index >38-folds vs. murine and human macrohages). For the glycosyl selenylsulfides, the anti-trypanosomal activity was not significantly influenced by the nature of the moiety attached to the sulfur atom. Except for a quinoline-, and to a minor extent a nitro-derivative, the most selective hits induced a rapid (within 60 min) and marked perturbation of the LMWTredox homeostasis. The formation of selenenylsulfide glycoconjugates with free thiols has been identified as a potential mechanism involved in this process.}, keywords = {MACROPHAGE; Selenoglycosides; Redox biosensor; Oxidative stress; Bloodstream trypanosoma}, year = {2024}, eissn = {2211-3207}, orcid-numbers = {Dibello, Estefanía/0000-0001-6378-3899; Oddone, Natalia/0009-0006-4884-9398; Kiss, Attila/0000-0003-3601-5143; Comini, Marcelo A./0000-0001-5000-1333} } @article{MTMT:34646990, title = {JE-133 Suppresses LPS-Induced Neuroinflammation Associated with the Regulation of JAK/STAT and Nrf2 Signaling Pathways}, url = {https://m2.mtmt.hu/api/publication/34646990}, author = {Tao, Lingxue and Yu, Weichen and Liu, Ziyi and Zhao, Danfeng and Lin, Sijin and Vargáné Szalóki, Dóra and Kicsák, Máté and Kurtán, Tibor and Zhang, Haiyan}, doi = {10.1021/acschemneuro.3c00454}, journal-iso = {ACS CHEM NEUROSCI}, journal = {ACS CHEMICAL NEUROSCIENCE}, volume = {15}, unique-id = {34646990}, issn = {1948-7193}, abstract = {Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, and interrupting the microglial-mediated neuroinflammation has been suggested as a promising strategy to delay or prevent the progression of neurodegeneration. In this study, we investigated the effects of JE-133, an optically active isochroman-2H-chromene conjugate containing a 1,3-disubstituted isochroman unit, on lipopolysaccharide (LPS)-induced microglial neuroinflammation and underlying mechanisms both in vitro and in vivo. First, JE-133 treatment decreased LPS-induced overproduction of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitrite, and nitric oxide synthase (iNOS) in BV2 microglial cells. Further study revealed that JE-133 downregulated the phosphorylation level of JAK/STAT and upregulated the protein level of Nrf2/HO-1 in LPS-stimulated BV2 microglial cells and verified that JE-133 directly bound to Keap1 by a pull-down assay. Next, JE-133 administration also inhibited neuroinflammation in vivo, as indicated by a reduced CD11b protein level and an overexpressed mRNA level of the pro-inflammatory cytokine TNF-α in the hippocampus of LPS-injected mice. Moreover, the regulative effects of JE-133 on the JAK/STAT and Nrf2/HO-1 pathways were also verified in the hippocampus of LPS-injected mice. Taken together, our study for the first time reports that JE-133 exhibits inhibitory effects against LPS-stimulated neuroinflammation both in vitro and in vivo, which might be associated with the simultaneous regulation of the JAK/STAT and Nrf2 pathways. Our findings may provide important clues for the discovery of effective drug leads/candidates against neuroinflammation-associated neurodegeneration.}, keywords = {neuroinflammation; microglia; LPS; Nrf2; JAK/STAT}, year = {2024}, eissn = {1948-7193}, pages = {258-267} } @article{MTMT:34567562, title = {Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein}, url = {https://m2.mtmt.hu/api/publication/34567562}, author = {Hőgye, Fanni and Farkas, László Bence and Balogh, Álex Kálmán and Szilágyi, László and Alnukari, Samar and Bajza, István and Borbás, Anikó and Fehér, Krisztina and Tóthné Illyés, Tünde Zita and Timári, István}, doi = {10.3390/ijms25031742}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34567562}, issn = {1661-6596}, abstract = {Human Galectin-3 (hGal-3) is a protein that selectively binds to β-galactosides and holds diverse roles in both normal and pathological circumstances. Therefore, targeting hGal-3 has become a vibrant area of research in the pharmaceutical chemistry. As a step towards the development of novel hGal-3 inhibitors, we synthesized and investigated derivatives of thiodigalactoside (TDG) modified with different aromatic substituents. Specifically, we describe a high-yielding synthetic route of thiodigalactoside (TDG); an optimized procedure for the synthesis of the novel 3,3′-di-O-(quinoline-2-yl)methyl)-TDG and three other known, symmetric 3,3′-di-O-TDG derivatives ((naphthalene-2yl)methyl, benzyl, (7-methoxy-2H-1-benzopyran-2-on-4-yl)methyl). In the present study, using competition Saturation Transfer Difference (STD) NMR spectroscopy, we determined the dissociation constant (Kd) of the former three TDG derivatives produced to characterize the strength of the interaction with the target protein (hGal-3). Based on the Kd values determined, the (naphthalen-2-yl)methyl, the (quinolin-2-yl)methyl and the benzyl derivatives bind to hGal-3 94, 30 and 24 times more strongly than TDG. Then, we studied the binding modes of the derivatives in silico by molecular docking calculations. Docking poses similar to the canonical binding modes of well-known hGal-3 inhibitors have been found. However, additional binding forces, cation–π interactions between the arginine residues in the binding pocket of the protein and the aromatic groups of the ligands, have been established as significant features. Our results offer a molecular-level understanding of the varying affinities observed among the synthesized thiodigalactoside derivatives, which can be a key aspect in the future development of more effective ligands of hGal-3.}, keywords = {lectin; NMR spectroscopy; Galectin-3; Molecular docking; STD NMR; thiodigalactosides}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547} } @article{MTMT:34510717, title = {Dynamic Structures of Bioactive Proteins as Determined by Nuclear Magnetic Resonance}, url = {https://m2.mtmt.hu/api/publication/34510717}, author = {Tőke, Orsolya and Batta, Gyula}, doi = {10.3390/ijms25010295}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34510717}, issn = {1661-6596}, abstract = {According to “Panta rhei”, a phrase by the ancient Greeks, you cannot enter the same river two times [...]}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Tőke, Orsolya/0000-0002-1741-1573; Batta, Gyula/0000-0002-0442-1828} } @article{MTMT:34528813, title = {Exo-glikál származékok átalakításainak a vizsgálata: tioladdíciós és cikloaddíciós reakciók}, url = {https://m2.mtmt.hu/api/publication/34528813}, author = {József, János and Somsák, László and Juhász, László}, doi = {10.24100/MKF.2023.03-04.147}, journal-iso = {MAGY KÉM FOLY KÉM KÖZL}, journal = {MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-)}, volume = {129}, unique-id = {34528813}, issn = {1418-9933}, year = {2023}, eissn = {1418-8600}, pages = {147-154}, orcid-numbers = {Somsák, László/0000-0002-9103-9845; Juhász, László/0000-0002-7462-7944} }