TY - JOUR AU - Homolya, Levente AU - Mathomes, Rachel T. AU - Fodor-Varga, Luca Anna AU - Docsa, Tibor AU - Juhász, László AU - Hayes, Joseph M. AU - Somsák, László TI - 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 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 9 SP - 1 EP - 21 PG - 21 SN - 1661-6596 DO - 10.3390/ijms25094591 UR - https://m2.mtmt.hu/api/publication/34813914 ID - 34813914 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Simons, Viktor E. AU - Mándi, Attila AU - Frank, Marian AU - van Geelen, Lasse AU - Tran-Cong, Nam AU - Albrecht, Dorothea AU - Coort, Annika AU - Gebhard, Christina AU - Kurtán, Tibor AU - Kalscheuer, Rainer TI - Colletodiol derivatives of the endophytic fungus Trichocladium sp. JF - FITOTERAPIA J2 - FITOTERAPIA VL - 175 PY - 2024 PG - 10 SN - 0367-326X DO - 10.1016/j.fitote.2024.105914 UR - https://m2.mtmt.hu/api/publication/34804043 ID - 34804043 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Wennrich, Jan-Peer AU - Ebada, Sherif S. AU - Sepanian, Ellen AU - Holzenkamp, Caren AU - Khalid, Syeda J. AU - Schrey, Hedda AU - Maier, Wolfgang AU - Mándi, Attila AU - Kurtán, Tibor AU - Ashrafi, Samad AU - Stadler, Marc TI - Omnipolyphilins A and B: Chlorinated Cyclotetrapeptides and Naphtho-α-pyranones from the Plant Nematode-Derived Fungus Polyphilus sieberi JF - JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY J2 - J AGR FOOD CHEM VL - 72 PY - 2024 IS - 13 SP - 6998 EP - 7009 PG - 12 SN - 0021-8561 DO - 10.1021/acs.jafc.4c00572 UR - https://m2.mtmt.hu/api/publication/34795040 ID - 34795040 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Dibello, Estefanía AU - Oddone, Natalia AU - Franco, Jaime AU - Tóthné Illyés, Tünde Zita AU - Medeiros, Andrea AU - Kiss, Attila AU - Hőgye, Fanni AU - E Kövér, Katalin AU - Szilágyi, László AU - Comini, Marcelo A. TI - Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity JF - INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE J2 - INT J PARASITOL-DRUG VL - 24 PY - 2024 PG - 6 SN - 2211-3207 DO - 10.1016/j.ijpddr.2024.100529 UR - https://m2.mtmt.hu/api/publication/34743720 ID - 34743720 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Hőgye, Fanni AU - Farkas, László Bence AU - Balogh, Álex Kálmán AU - Szilágyi, László AU - Alnukari, Samar AU - Bajza, István AU - Borbás, Anikó AU - Fehér, Krisztina AU - Tóthné Illyés, Tünde Zita AU - Timári, István TI - Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 3 PG - 18 SN - 1661-6596 DO - 10.3390/ijms25031742 UR - https://m2.mtmt.hu/api/publication/34567562 ID - 34567562 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Tőke, Orsolya AU - Batta, Gyula TI - Dynamic Structures of Bioactive Proteins as Determined by Nuclear Magnetic Resonance JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 PG - 6 SN - 1661-6596 DO - 10.3390/ijms25010295 UR - https://m2.mtmt.hu/api/publication/34510717 ID - 34510717 AB - According to “Panta rhei”, a phrase by the ancient Greeks, you cannot enter the same river two times [...] LA - English DB - MTMT ER - TY - JOUR AU - József, János AU - Somsák, László AU - Juhász, László TI - Exo-glikál származékok átalakításainak a vizsgálata: tioladdíciós és cikloaddíciós reakciók JF - MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-) J2 - MAGY KÉM FOLY KÉM KÖZL VL - 129 PY - 2023 IS - 3-4 SP - 147 EP - 154 PG - 8 SN - 1418-9933 DO - 10.24100/MKF.2023.03-04.147 UR - https://m2.mtmt.hu/api/publication/34528813 ID - 34528813 N1 - A közlemény József János PhD értekezéséhez kapcsolódó tézisfüzet alapján készült; a kutatás a GINOP-2.3.2.-15-2016-00008 és a GINOP-2.3.3-15-2016-00004 számú projektek keretében, az Európai Unió támogatásával, az Európai Regionális Fejlesztési Alap, valamint a Nemzeti, Kutatási, Fejlesztési és Innovációs Hivatal (NKFIH) FK128766 számú pályázat támogatásával valósult meg. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Sum, Winnie Chemutai AU - Ebada, Sherif S. AU - Kirchenwitz, Marco AU - Wanga, Lucy AU - Decock, Cony AU - Stradal, Theresia E. B. AU - Matasyoh, Josphat Clement AU - Mándi, Attila AU - Kurtán, Tibor AU - Stadler, Marc TI - Neurite Outgrowth-Inducing Drimane-Type Sesquiterpenoids Isolated from Cultures of the Polypore Abundisporus violaceus MUCL 56355 JF - JOURNAL OF NATURAL PRODUCTS J2 - J NAT PROD VL - 86 PY - 2023 IS - 11 SP - 2457 EP - 2467 PG - 11 SN - 0163-3864 DO - 10.1021/acs.jnatprod.3c00525 UR - https://m2.mtmt.hu/api/publication/34443271 ID - 34443271 AB - Abundisporin A (1), together with seven previously undescribed drimane sesquiterpenes named abundisporins B-H (2-8), were isolated from a polypore, Abundisporus violaceus MUCL 56355 (Polyporaceae), collected in Kenya. Chemical structures of the isolated compounds were elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by HRESIMS data. The absolute configurations of the isolated compounds were determined by using Mosher’s method for 1-4 and TDDFT-ECD calculations for 4 and 5-8. None of the isolated compounds exhibited significant activities in either antimicrobial or cytotoxicity assays. Notably, all of the tested compounds demonstrated neurotrophic effects, with 1 and 6 significantly increasing outgrowth of neurites when treated with 5 ng/mL NGF. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Erzsébet AU - Balázs, Viktória Lilla AU - Sándor, Viktor AU - Agócs, Attila AU - Nagy, Veronika AU - Király, Sándor Balázs AU - Kurtán, Tibor AU - Molnár, Péter AU - Deli, József TI - Carotenoid Composition of Telekia speciosa JF - PLANTS-BASEL J2 - PLANTS-BASEL VL - 12 PY - 2023 IS - 24 PG - 12 SN - 2223-7747 DO - 10.3390/plants12244116 UR - https://m2.mtmt.hu/api/publication/34429989 ID - 34429989 N1 - Department of Pharmacognosy and Phytotherapy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Târgu Mureș, 540139, Romania Department of Pharmacognosy, Faculty of Pharmacy, University of Pécs, Rókus utca 2, Pécs, H-7624, Hungary Institute of Bioanalysis, Medical School, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, Pécs, H-7624, Hungary Department of Organic Chemistry, Faculty of Sciences, University of Debrecen, Debrecen, H-4032, Hungary Export Date: 8 January 2024 Correspondence Address: Deli, J.; Department of Pharmacognosy, Rókus utca 2, Hungary; email: jozsef.deli@aok.pte.hu AB - The carotenoid composition of the flower of Telekia speciosa was investigated for the first time by HPLC-DAD-MS. In addition to the main carotenoid lutein and its geometrical isomers, 5,6-epoxy-carotenoids, namely violaxanthin, lutein 5,6-epoxide and antheraxanthin, were detected in larger amounts. In addition, β-carotene 5,6-epoxide and β-carotene 5,6,5′,6′-diepoxide were found, which occurs very rarely in plants. For unambigous identification, β-carotene 5,6-epoxide and β-carotene 5,6,5′,6′-diepoxide were prepared semisynthetically, and they were characterized by 1H and 13C NMR and HPLC-CD methods. LA - English DB - MTMT ER - TY - JOUR AU - Anwar, Alaa AU - Elnaggar, Mohamed S. AU - Elissawy, Ahmed M. AU - Ibrahim, Nehal AU - Mándi, Attila AU - Kurtán, Tibor AU - Liu, Zhen AU - El-Ahmady, Sherweit H. AU - Kalscheuer, Rainer TI - New Meroterpenoid Derivatives from the Pomegranate-Derived Endophytic Fungus Talaromyces purpureogenus JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 22 PG - 12 SN - 1420-3049 DO - 10.3390/molecules28227650 UR - https://m2.mtmt.hu/api/publication/34401134 ID - 34401134 AB - In this study, we report the isolation of two new meroterpenoids, miniolutelide D (1) and miniolutelide E (13-epi-miniolutelide C) (2), along with two meroterpenoidal analogues (3 and 4) and two phenolic compounds (5 and 6) from the endophytic fungus Talaromyces purpureogenus derived from Punica granatum fruits. Their structures were elucidated using extensive MS, 1D, and 2D NMR spectroscopic analyses as well as by comparing with data in the literature. The absolute configurations of 1 and 2 were determined using TDDFT-ECD calculations. Antimicrobial activity was evaluated. Compound 5 displayed significant activity against methicillin-resistant Staphylococcus aureus strain ATCC 700699 and moderate activity against S. aureus strain ATCC 29213. LA - English DB - MTMT ER -