TY - JOUR AU - Kaszás, Tímea AU - Szakács, Bence AU - Blága, Tekla AU - Doherty, Kyle AU - Keenan-Dillon, Rachel AU - Reynolds, Shauna AU - Kavanagh, Kevin AU - Velasco-Torrijos, Trinidad AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Synthesis of mono- and di-(C-glycopyranosyl-isoxazol(in)yl) derivatives on aromatic scaffolds and their evaluation as anti-adherence agents of Candida albicans JF - FRONTIERS IN CHEMISTRY J2 - FRONT CHEM VL - 14 PY - 2026 SP - 1 EP - 14 PG - 14 SN - 2296-2646 DO - 10.3389/fchem.2026.1794047 UR - https://m2.mtmt.hu/api/publication/37099528 ID - 37099528 AB - The yeast Candida albicans is one of the most prevalent fungal pathogens. It induces superficial and systemic infections in immunocompromised patients. The high pathogenicity of Candida species may be related to their adherence to the host tissues. Cell surface glycans are important receptors for C. albicans and warrant the development of anti-adherence ligands that can mimic them and disrupt C. albicans –epithelial cell interactions. A divalent galactoside glycomimetic containing 1,2,3-triazole units was found to be one of the most potent inhibitors of C. albicans adhesion to exfoliated buccal epithelial cells. Based on this lead molecule, herein we report on the synthesis and evaluation of a new series of mono- and divalent glycosides, featuring isophthalamide and benzene scaffolds with C -glycosyl isoxazoline and isoxazole, as well as N -glycosyl 1,2,3-triazole units. The new compounds were obtained by 1,3-dipolar cycloaddition reactions between the above scaffolds functionalized with one or two alkenyl or alkynyl moieties and glycosyl nitrile oxides and glycosyl azides, respectively. The tested deprotected compounds were non-toxic to the C. albicans cells and exhibited significant inhibition of C. albicans adhesion, showing good and moderate inhibition in exclusion and competitive assays, respectively. This study demonstrated the utility of isoxazole/isoxazoline heterocycles to replace 1,2,3-triazoles in aromatic-core glycoconjugates to furnish anti-adhesion molecules equipotent with the lead and also showed that the simple benzene core can serve well in potential anti-adhesives against C. albicans . LA - English DB - MTMT ER - TY - JOUR AU - Salama, Alshimaa Ibrahim Zaki Ahmed AU - Sipos, Adrienn AU - Kacsir, István AU - Kovács, N. I. AU - Kerekes, Éva AU - Szoták, E. AU - Freytag, Csongor AU - Demény, Máté Ágoston AU - Révész, I. AU - Buglyó, Péter AU - Bényei, Attila Csaba AU - Janka, Eszter Anna AU - Kardos, Gábor AU - Somsák, László AU - Bay, Péter AU - Bokor, Éva TI - Platinum-group metal half-sandwich complexes of 1-(alpa-D-glucopyranosyl)-4-hetaryl-1,2,3-triazoles : synthesis, solution equilibrium studies and investigation of their anticancer and antimicrobial activitie JF - FRONTIERS IN CHEMISTRY J2 - FRONT CHEM VL - 13 PY - 2025 PG - 23 SN - 2296-2646 DO - 10.3389/fchem.2025.1619991 UR - https://m2.mtmt.hu/api/publication/36285838 ID - 36285838 AB - Although platinum-based complexes are pivotal in chemotherapy, their clinical use is limited by toxicity and resistance. Previously, we identified a set of osmium, ruthenium, and iridium half-sandwich complexes of 1- N -(β- d -glucopyranosyl)-4-hetaryl-1,2,3-triazole-type N,N-chelators with potent and selective activity against a large set of diverse neoplasia cell models and multiresistant Gram-positive bacteria (methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE)). Our aim in this study was to assess how the configuration of the C1 carbon in the glucose moiety affects the biological activity of the complexes. Thus, 1- N -(α- d -glucopyranosyl)-4-hetaryl-1,2,3-triazoles were synthesized and used as N,N-bidentate ligands to result in half-sandwich type complexes analogous to the earlier reported ones. Overall, the newly prepared complexes with the α-anomeric carbohydrate moiety had similar biological properties to the complexes with the β-anomeric carbohydrate unit in terms of their biological activity on cancer cells or primary human cells. Importantly, the bacteriostatic property of the complexes with an α-anomeric sugar moiety was inferior to that of the complexes containing the β-anomer. LA - English DB - MTMT ER - TY - JOUR AU - Akel, Rahaf AU - Salama, Alshimaa Ibrahim Zaki Ahmed AU - Kerekes, Éva AU - Kacsir, István AU - Kiss, György Attila AU - Freytag, Csongor AU - Szoták, Evelin AU - Boros-Pál, Dóra AU - Janka, Eszter Anna AU - Kardos, Gábor AU - Bay, Péter AU - Somsák, László AU - Kun, Sándor AU - Sipos, Adrienn AU - Bokor, Éva TI - Platinum-group metal half-sandwich complexes with C-glucopyranosyl 1,2,3-triazoles and isoxazoles as ligands: synthesis and evaluation as antineoplastic and antimicrobial agents JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 215 PY - 2025 SP - 1 EP - 20 PG - 20 SN - 0928-0987 DO - 10.1016/j.ejps.2025.107259 UR - https://m2.mtmt.hu/api/publication/36323150 ID - 36323150 AB - Half-sandwich complexes of platinum-group metals are a widely studied subgroup of organometallic compounds with promising anticancer and antimicrobial properties. Recently, we have published a set of polyhapto arene/arenyl Ru(II), Os(II), Ir(III) and Rh(III) complexes with hetaryl-substituted 1-N-glucopyranosyl-1,2,3-triazole and C-glycopyranosyl-1,3,4- and -1,2,4-oxadiazole-type N,N-bidentate ligands, several of which exhibited (sub)micromolar antineoplastic and bacteriostatic potencies. The structure-activity relationships of these series indicated that the nature of the azole ring and its way of connection to the pyranoid sugar unit played crucial roles in the biological activity of such complexes. In order to further study the influence of the five-membered heteroaromatic moiety, in this work we have synthesised new complexes with O-protected 4-C-(β-D-glucopyranosyl)-1-(pyridin-2-yl)-1,2,3-triazoles and 5-C-(β-D-glucopyranosyl)-3-(pyridin-2-yl)-isoxazoles as N,N-chelating ligands of η6-p-cymRu(II)/Os(II) and η5-Cp*-Ir(III)/Rh(III) complexes and have studied their cytostatic and antibacterial properties. All but the Rh(III)-derived complexes exerted cytostasis on a plethora of neoplasia cell models. The Ru(II)- and Os(II)-based complexes had the best IC50 values. The isoxazole-containing compounds outperformed the triazole-containing ones in terms of their cytostatic properties with submicromolar IC50 values. A subset of the complexes with Ru(II) and Ir(III) ions had bacteriostatic properties with low micromolar MIC values. LA - English DB - MTMT ER - TY - JOUR AU - Akel, Rahaf AU - Kacsir, István AU - Kerekes, Éva AU - Freytag, Csongor AU - Szoták, Evelin AU - Boros-Pál, Dóra AU - Janka, Eszter Anna AU - Bényei, Attila Csaba AU - Kardos, Gábor AU - Bokor, Éva AU - Somsák, László AU - Bay, Péter AU - Sipos, Adrienn AU - Kun, Sándor TI - Platinum-group metal half-sandwich complexes of sugar-isoxazol(in)e conjugates – synthesis and evaluation of their antineoplastic and antimicrobial activities JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 215 PY - 2025 PG - 18 SN - 0928-0987 DO - 10.1016/j.ejps.2025.107260 UR - https://m2.mtmt.hu/api/publication/36323399 ID - 36323399 AB - Platinum-group metal half-sandwich complexes are considered to be potential replacements of the clinically widely used platins which have several side effects and tend to cause resistance to develop. In our previous works, we used a range of 2-pyridyl-substituted N- and C-glycosyl heterocycles as N,N-chelating ligands to prepare ruthenium(II), osmium(II), iridium(III) and rhodium(III) polyhapto arene/arenyl half-sandwich complexes. Some of these complexes, particularly with the C-glucopyranosyl isoxazole derived ligand in its Operbenzoylated form, exhibited greater anticancer efficiency than cisplatin and had minimal or negligible effects on non-transformed fibroblasts. Additionally, these cytostatic compounds exhibited micromolar antibacterial activity against multiresistant Gram-positive bacteria. In the present work, novel modes of conjugation between the sugar and the isoxazole moieties have been studied. Specifically, glycosylidene-spiro-isoxazoline and polyhydroxyalkylisoxazole scaffolds were synthesised and utilised in complex formation reactions. The spiro-isoxazolines were obtained in 1,3-dipolar cycloadditions of exo-glycals and nitrile oxides generated from pyridine-2-carbaldoximes. Ring opening of the spiroisoxazolines under basic or transition-metal-mediated conditions produced polyhydroxyalkylisoxazoles. These compounds were then transformed into their Operacetylated, O-perbenzoylated and O-unprotected variants, which were used for complex formation with the above-mentioned platinum-group metal ions. The complexes induced cytostasis in cellular models of ovarian cancer and pancreatic adenocarcinoma; the best compounds had submicromolar IC50 values (0.4-0.5 µM). A subset of the cytostatic complexes retained their activity on cisplatin resistant ovarian cancer cells. Furthermore, a reasonable therapeutic index was detected when complexes were assessed on primary human fibroblasts pointing towards a potential applicability of the complexes. Unexpectedly, none of the complexes induced bacteriostasis in Gram-positive bacteria as Staphylococcus aureus or Enterococcus species. LA - English DB - MTMT ER - TY - JOUR AU - Szakács, Bence AU - Kaszás, Tímea AU - Juhászné Tóth, Éva AU - Cservenyak, Ivett AU - Timári, István AU - Nilsson, Ulf J. AU - Fodor-Varga, Luca Anna AU - Docsa, Tibor AU - Molnar, Viktoria AU - Kulcsar, Andrea Eniko AU - Marton, Lili AU - Kónya-Ábrahám, Anita AU - Kiss, Attila AU - József, János AU - Juhász, László AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - A Regioselective Synthesis of 2,4-Disubstituted 2H-1,2,3-Triazoles by Coupling of N-Tosylhydrazones and Anhydro-Aldose Tosylhydrazones with 4-Substituted 1H-1,2,3-Triazoles - Scope and Limitations JF - ACS OMEGA J2 - ACS OMEGA VL - 10 PY - 2025 IS - 50 SP - 61370 EP - 61399 PG - 30 SN - 2470-1343 DO - 10.1021/acsomega.5c06151 UR - https://m2.mtmt.hu/api/publication/36523617 ID - 36523617 AB - In this paper we present the first investigation of the C-N coupling reaction between N-tosylhydrazones including Operacylated 2,6-anhydro-aldose tosylhydrazones and 1H-1,2,3-triazoles under catalyst-free conditions. This transformation is characterized by relatively mild thermal conditions, high regioselectivity in favor of 2,4-disubstituted 2H-1,2,3-triazoles and broad functional group tolerance as well as applicability in medicinal chemistry due to the absence of transition metal residues. Tosylhydrazones of aldehydes showed better results in terms of yields (20-61%) than those of ketones (13-16%). From the 1,2,3-triazole side the reactions gave very good results in terms of regioselectivity with both electron-withdrawing and electron-donating groups in the 4-position aromatic substituents, while benzotriazoles proved unselective. The extension of the reaction to 2,6-anhydro-aldose tosylhydrazones retained the excellent regioselectivity with high yields, to provide a new synthetic pathway for 2-glycosylmethyl-4-substituted-2H-1,2,3-triazoles, a novel type of glycomimetics. The carbohydrate derivatives were evaluated as potential galectin-1 antagonists and glycogen phosphorylase enzyme inhibitors. In addition to classical 1H and 13C NMR characterizations, advanced 1H-15N multiple-bond correlation NMR experiments were also performed on some glycomimetics to get direct evidence for the regioisomer synthesized. LA - English DB - MTMT ER - 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 - CONF AU - Ecsedi, Zoárd AU - Shafique, Hina AU - Szakács, Bence AU - Kaszás, Tímea AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Glikopiranozilidén-spiro-izoxazolinok, mint potenciális Candida Albicans ellenes szerek szintézise T2 - Vegyészkonferencia 2024 Program és Előadásösszefoglalók SN - 9786156018243 PY - 2024 SP - 68, P-7 UR - https://m2.mtmt.hu/api/publication/35573748 ID - 35573748 N1 - A kutatást a Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal támogatta a PD 142641 projekt keretében. LA - Hungarian DB - MTMT ER - TY - CONF AU - Kaszás, Tímea AU - Szakács, Bence AU - Bertalan, Márta AU - Lengyel, Ákos AU - Hameed, Faria AU - Blága, Tekla AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Anhidro-aldóz oximok cikloaddíciós reakcióinak vizsgálata Cycloaddition reactions of anhydro-aldose oximes T2 - XXX. Nemzetközi Vegyészkonferencia PB - Erdélyi Magyar Műszaki Tudományos Társaság (EMT) C1 - Kolozsvár T3 - Nemzetközi Vegyészkonferencia, ISSN 1843-6293 ; 30. PY - 2024 UR - https://m2.mtmt.hu/api/publication/35573807 ID - 35573807 N1 - Poszter, P-11 A kutatás a Nemzeti Kutatási, Fejlesztési és Innovációs Hivatal PD 142641 számú pályázat támogatásával, és a COST CA18132 számú pályázat támogatásával készült. LA - Hungarian DB - MTMT ER - TY - GEN AU - Kaszás, Tímea AU - Szakács, Bence AU - Bertalan, Márta AU - Lengyel, Ákos AU - Hameed, Faria AU - Blága, Tekla AU - Bay, Péter AU - Nilsson, J. Ulf AU - Somsák, László AU - Vágvölgyiné Tóth, Marietta TI - Anhidro-aldóz oximok szintézise és cikloaddíciós reakcióinak vizsgálata PY - 2024 UR - https://m2.mtmt.hu/api/publication/35649155 ID - 35649155 N1 - Előadás The research was supported by the National Research, Development and Innovation Office under the project PD 142641. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Bokor, Éva AU - Kecskes, Dora T. AU - Gombas, Ferenc AU - Feher, Alexandra AU - Kardos, Eszter AU - Dabian, Akram AU - Vonza, Zsofia AU - Szennyes, Eszter AU - Somsák, László TI - First representatives of C-glycosyl 1,2,4,5-tetrazines: synthesis of 3-beta-d-glucopyranosyl 1,2,4,5-tetrazines and their transformation into 3-beta-d-glucopyranosyl pyridazines JF - NEW JOURNAL OF CHEMISTRY J2 - NEW J CHEM VL - 47 PY - 2023 IS - 1 SP - 56 EP - 74 PG - 19 SN - 1144-0546 DO - 10.1039/d2nj03920f UR - https://m2.mtmt.hu/api/publication/33320709 ID - 33320709 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary; [OTKA FK 125067] AB - 1,2,4,5-Tetrazines (s-tetrazines) are a long known class of compounds with many applications e.g. in heterocyclic syntheses and recently in bioorthogonal chemistry. C-Glycopyranosyl tetrazines are unknown in the literature, therefore, we have started to study their synthesis. In this paper ring closing reactions leading to s-tetrazines have been investigated with suitable beta-d-glucopyranosyl precursors and the feasible transformations have been identified. In addition, the obtained C-glucopyranosyl tetrazines' basic protecting group compatibility and their utility in inverse electron demand Diels-Alder cycloadditions towards a variety of C-glucopyranosyl pyridazines have been demonstrated. LA - English DB - MTMT ER -