@article{MTMT:36285838, title = {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}, url = {https://m2.mtmt.hu/api/publication/36285838}, author = {Salama, Alshimaa Ibrahim Zaki Ahmed and Sipos, Adrienn and Kacsir, István and Kovács, N. I. and Kerekes, Éva and Szoták, E. and Freytag, Csongor and Demény, Máté Ágoston and Révész, I. and Buglyó, Péter and Bényei, Attila Csaba and Janka, Eszter Anna and Kardos, Gábor and Somsák, László and Bay, Péter and Bokor, Éva}, doi = {10.3389/fchem.2025.1619991}, journal-iso = {FRONT CHEM}, journal = {FRONTIERS IN CHEMISTRY}, volume = {13}, unique-id = {36285838}, issn = {2296-2646}, abstract = {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.}, year = {2025}, eissn = {2296-2646}, orcid-numbers = {Freytag, Csongor/0000-0002-3356-4182; Buglyó, Péter/0000-0002-6714-7598; Janka, Eszter Anna/0000-0003-0724-5281; Somsák, László/0000-0002-9103-9845} } @article{MTMT:36323150, title = {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}, url = {https://m2.mtmt.hu/api/publication/36323150}, author = {Akel, Rahaf and Salama, Alshimaa Ibrahim Zaki Ahmed and Kerekes, Éva and Kacsir, István and Kiss, György Attila and Freytag, Csongor and Szoták, Evelin and Boros-Pál, Dóra and Janka, Eszter Anna and Kardos, Gábor and Bay, Péter and Somsák, László and Kun, Sándor and Sipos, Adrienn and Bokor, Éva}, doi = {10.1016/j.ejps.2025.107259}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, volume = {215}, unique-id = {36323150}, issn = {0928-0987}, abstract = {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.}, keywords = {cytostasis; 1,2,3-Triazole; Isoxazole; bacteriostasis; Half-sandwich complex; C-glycosyl derivative}, year = {2025}, eissn = {1879-0720}, pages = {1-20}, orcid-numbers = {Freytag, Csongor/0000-0002-3356-4182; Janka, Eszter Anna/0000-0003-0724-5281; Somsák, László/0000-0002-9103-9845} } @article{MTMT:36323399, title = {Platinum-group metal half-sandwich complexes of sugar-isoxazol(in)e conjugates – synthesis and evaluation of their antineoplastic and antimicrobial activities}, url = {https://m2.mtmt.hu/api/publication/36323399}, author = {Akel, Rahaf and Kacsir, István and Kerekes, Éva and Freytag, Csongor and Szoták, Evelin and Boros-Pál, Dóra and Janka, Eszter Anna and Bényei, Attila Csaba and Kardos, Gábor and Bokor, Éva and Somsák, László and Bay, Péter and Sipos, Adrienn and Kun, Sándor}, doi = {10.1016/j.ejps.2025.107260}, journal-iso = {EUR J PHARM SCI}, journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, unique-id = {36323399}, issn = {0928-0987}, abstract = {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.}, keywords = {cytostasis; Isoxazole; Isoxazoline; spiro-compound; Half-sandwich complex; Platinum-group metal; Monosaccharide derivative}, year = {2025}, eissn = {1879-0720}, pages = {107260}, orcid-numbers = {Freytag, Csongor/0000-0002-3356-4182; Janka, Eszter Anna/0000-0003-0724-5281; Somsák, László/0000-0002-9103-9845} } @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} } @CONFERENCE{MTMT:35573748, title = {Glikopiranozilidén-spiro-izoxazolinok, mint potenciális Candida Albicans ellenes szerek szintézise}, url = {https://m2.mtmt.hu/api/publication/35573748}, author = {Ecsedi, Zoárd and Shafique, Hina and Szakács, Bence and Kaszás, Tímea and Somsák, László and Vágvölgyiné Tóth, Marietta}, booktitle = {Vegyészkonferencia 2024 Program és Előadásösszefoglalók}, unique-id = {35573748}, year = {2024}, pages = {68, P-7}, orcid-numbers = {Szakács, Bence/0000-0002-9157-3028; Somsák, László/0000-0002-9103-9845} } @CONFERENCE{MTMT:35573807, title = {Anhidro-aldóz oximok cikloaddíciós reakcióinak vizsgálata Cycloaddition reactions of anhydro-aldose oximes}, url = {https://m2.mtmt.hu/api/publication/35573807}, author = {Kaszás, Tímea and Szakács, Bence and Bertalan, Márta and Lengyel, Ákos and Hameed, Faria and Blága, Tekla and Somsák, László and Vágvölgyiné Tóth, Marietta}, booktitle = {XXX. Nemzetközi Vegyészkonferencia}, unique-id = {35573807}, year = {2024}, orcid-numbers = {Szakács, Bence/0000-0002-9157-3028; Somsák, László/0000-0002-9103-9845} } @misc{MTMT:35649155, title = {Anhidro-aldóz oximok szintézise és cikloaddíciós reakcióinak vizsgálata}, url = {https://m2.mtmt.hu/api/publication/35649155}, author = {Kaszás, Tímea and Szakács, Bence and Bertalan, Márta and Lengyel, Ákos and Hameed, Faria and Blága, Tekla and Bay, Péter and Nilsson, J. Ulf and Somsák, László and Vágvölgyiné Tóth, Marietta}, unique-id = {35649155}, year = {2024}, orcid-numbers = {Szakács, Bence/0000-0002-9157-3028; Somsák, László/0000-0002-9103-9845} } @article{MTMT:33320709, title = {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}, url = {https://m2.mtmt.hu/api/publication/33320709}, author = {Bokor, Éva and Kecskes, Dora T. and Gombas, Ferenc and Feher, Alexandra and Kardos, Eszter and Dabian, Akram and Vonza, Zsofia and Szennyes, Eszter and Somsák, László}, doi = {10.1039/d2nj03920f}, journal-iso = {NEW J CHEM}, journal = {NEW JOURNAL OF CHEMISTRY}, volume = {47}, unique-id = {33320709}, issn = {1144-0546}, abstract = {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.}, year = {2023}, eissn = {1369-9261}, pages = {56-74}, orcid-numbers = {Somsák, László/0000-0002-9103-9845} } @article{MTMT:33652227, title = {Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria}, url = {https://m2.mtmt.hu/api/publication/33652227}, author = {Kacsir, István and Sipos, Adrienn and Kiss, Tímea and Major, Evelin and Bajusz, Nikolett and Tóth, Emese and Buglyó, Péter and Somsák, László and Kardos, Gábor and Bay, Péter and Bokor, Éva}, doi = {10.3389/fchem.2023.1086267}, journal-iso = {FRONT CHEM}, journal = {FRONTIERS IN CHEMISTRY}, volume = {11}, unique-id = {33652227}, issn = {2296-2646}, abstract = {The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC 50 value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC 50 value of the complexes. The complexes containing [(η 6 - p -cymene)Ru(II)], [(η 6 - p -cymene)Os(II)] or [(η 5 -Cp*)Ir(III)] were biologically active unlike the complex containing [(η 5 -Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC 50 values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positive Enterococcus and Staphylococcus aureus isolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.}, keywords = {SARCOMA; Ovarian cancer; VRE; MRSA; QUINOLINE; reactive oxygen species production; Half-sandwich complex; glycosyl triazole}, year = {2023}, eissn = {2296-2646}, orcid-numbers = {Buglyó, Péter/0000-0002-6714-7598; Somsák, László/0000-0002-9103-9845} } @article{MTMT:33678042, title = {[2+2] Cycloadditions of Methylene exo ‐Glycals: Synthesis of Glycopyranosylidene‐Spiro‐Azetidine‐2‐ones (β‐Lactams) and Cyclobutanones}, url = {https://m2.mtmt.hu/api/publication/33678042}, author = {József, János and Somsák, László and Vágvölgyiné Tóth, Marietta and Juhász, László}, doi = {10.1002/ejoc.202201488}, journal-iso = {EUR J ORG CHEM}, journal = {EUROPEAN JOURNAL OF ORGANIC CHEMISTRY}, volume = {26}, unique-id = {33678042}, issn = {1434-193X}, abstract = {[2+2] Cycloadditions of methylene exo-glycal derivatives with chlorosulfonyl isocyanate and dichloroketene were studied in detail, investigating the effect of the carbohydrate moiety, protecting groups as well as reaction temperature on the yields of the transformations. These reactions gave new anomeric spiro-β-lactam and spiro-cyclobutanone derivatives, whose structure was established by 1D and 2D NMR and MS experiments. The transformation of spiro-cyclobutanone into spiro-γ-lactone was also demonstrated.}, keywords = {CHLOROSULFONYL ISOCYANATE; cycloaddition; DICHLOROKETENE; exo-glycal; spiro-cyclobutanone; spiro-β-lactam}, year = {2023}, eissn = {1099-0690}, pages = {1-10}, orcid-numbers = {Somsák, László/0000-0002-9103-9845; Juhász, László/0000-0002-7462-7944} }