TY - JOUR AU - Tóth, Balázs István AU - Bahar, Bazeli AU - Annelies, Janssens AU - Lisztes, Erika AU - Racskó, Márk AU - Kelemen, Balázs AU - Herczeg, Mihály AU - Nagy, Tamás Milán AU - E Kövér, Katalin AU - Argha, Mitra AU - Attila, Borics AU - Bíró, Tamás AU - Thomas, Voets TI - Direct modulation of TRPM8 ion channels by rapamycin and analog macrolide immunosuppressants JF - ELIFE J2 - ELIFE PY - 2024 SN - 2050-084X UR - https://m2.mtmt.hu/api/publication/34722559 ID - 34722559 N1 - preprint DOI-ja: 10.1101/2024.02.01.578392 LA - English DB - MTMT ER - TY - JOUR AU - Herczeg, Mihály AU - Demeter, Fruzsina AU - Nagy, Tibor AU - Rusznyák, Ágnes AU - Hodek, Jan AU - Sipos, Éva AU - Lekli, István AU - Fenyvesi, Ferenc AU - Weber, Jan AU - Kéki, Sándor AU - Borbás, Anikó TI - Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 SN - 1661-6596 DO - 10.3390/ijms25010677 UR - https://m2.mtmt.hu/api/publication/34502650 ID - 34502650 AB - Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Eszter Boglárka AU - Herczeg, Mihály AU - Houser, Josef AU - Rievajová, Martina AU - Kuki, Ákos AU - Malinovská, Lenka AU - Naesens, Lieve AU - Wimmerová, Michaela AU - Borbás, Anikó AU - Herczegh, Pál AU - Bakai-Bereczki, Ilona TI - Amphiphilic Sialic Acid Derivatives as Potential Dual-Specific Inhibitors of Influenza Hemagglutinin and Neuraminidase JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 24 PG - 23 SN - 1661-6596 DO - 10.3390/ijms242417268 UR - https://m2.mtmt.hu/api/publication/34427826 ID - 34427826 AB - In the shadow of SARS-CoV-2, influenza seems to be an innocent virus, although new zoonotic influenza viruses evolved by mutations may lead to severe pandemics. According to WHO, there is an urgent need for better antiviral drugs. Blocking viral hemagglutinin with multivalent N-acetylneuraminic acid derivatives is a promising approach to prevent influenza infection. Moreover, dual inhibition of both hemagglutinin and neuraminidase may result in a more powerful effect. Since both viral glycoproteins can bind to neuraminic acid, we have prepared three series of amphiphilic self-assembling 2-thio-neuraminic acid derivatives constituting aggregates in aqueous medium to take advantage of their multivalent effect. One of the series was prepared by the azide-alkyne click reaction, and the other two by the thio-click reaction to yield neuraminic acid derivatives containing lipophilic tails of different sizes and an enzymatically stable thioglycosidic bond. Two of the three bis-octyl derivatives produced proved to be active against influenza viruses, while all three octyl derivatives bound to hemagglutinin and neuraminidase from H1N1 and H3N2 influenza types. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Eszter Boglárka AU - Tóth, Gergely AU - Spolárics, Júlia AU - Herczeg, Mihály AU - Hodek, Jan AU - Zupkó, István AU - Minorics, Renáta AU - Ádám, Dorottya AU - Oláh, Attila AU - Zouboulis, Christos C. AU - Weber, Jan AU - Nagy, Lajos AU - Ostorházi, Eszter AU - Bácskay, Ildikó AU - Borbás, Anikó AU - Herczegh, Pál AU - Bakai-Bereczki, Ilona TI - Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 20 SN - 2045-2322 DO - 10.1038/s41598-023-45565-7 UR - https://m2.mtmt.hu/api/publication/34316518 ID - 34316518 AB - (−)-Cannabidiol (CBD) and (−)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical and biological properties. In this study, Mannich-type reaction was used for the synthetic modification of CBD and CBG for the first time, and thus fifteen new cannabinoid derivatives containing one or two tertiary amino groups were prepared. Thereafter the antiviral, antiproliferative and antibacterial properties of the derivatives and their effects on certain skin cells were investigated. Some modified CBD derivatives showed remarkable antiviral activity against SARS-CoV-2 without cytotoxic effect, while synthetic modifications on CBG resulted in a significant increase in antiproliferative activity in some cases compared to the parent compound. LA - English DB - MTMT ER - TY - JOUR AU - Bege, Miklós AU - Herczeg, Mihály AU - Bakai-Bereczki, Ilona AU - Debreczeni, Nóra AU - Bényei, Attila Csaba AU - Herczegh, Pál AU - Borbás, Anikó TI - Triaza-tricyclanos – synthesis of a new class of tricyclic nucleoside analogues by stereoselective cascade cyclocondensation JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 21 PY - 2023 IS - 10 SP - 2213 EP - 2219 PG - 7 SN - 1477-0520 DO - 10.1039/D3OB00154G UR - https://m2.mtmt.hu/api/publication/33657380 ID - 33657380 AB - Conformationally constrained tricyclic morpholino-nucleosides containing three new chirality centers were prepared with full stereoselectivity, through two consecutive hemiaminal-imidazolidine cascade reactions. LA - English DB - MTMT ER - TY - JOUR AU - Demeter, Fruzsina AU - Török, Patrik AU - Kiss, Alexandra AU - Kovásznai-Oláh, Richárd AU - Máthéné Szigeti, Zsuzsa AU - Baksa, Viktória AU - Kovács, Fruzsina AU - Balla , Noémi AU - Fenyvesi, Ferenc AU - Váradi, Judit AU - Borbás, Anikó AU - Herczeg, Mihály TI - First Synthesis of DBU-Conjugated Cationic Carbohydrate Derivatives and Investigation of Their Antibacterial and Antifungal Activity JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 4 PG - 20 SN - 1661-6596 DO - 10.3390/ijms24043550 UR - https://m2.mtmt.hu/api/publication/33635459 ID - 33635459 AB - The emergence of drug-resistant bacteria and fungi represents a serious health problem worldwide. It has long been known that cationic compounds can inhibit the growth of bacteria and fungi by disrupting the cell membrane. The advantage of using such cationic compounds is that the microorganisms would not become resistant to cationic agents, since this type of adaptation would mean significantly altering the structure of their cell walls. We designed novel, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)-derived amidinium salts of carbohydrates, which may be suitable for disturbing the cell walls of bacteria and fungi due to their quaternary ammonium moiety. A series of saccharide-DBU conjugates were prepared from 6-iodo derivatives of d-glucose, d-mannose, d-altrose and d-allose by nucleophilic substitution reactions. We optimized the synthesis of a d-glucose derivative, and studied the protecting group free synthesis of the glucose-DBU conjugates. The effect of the obtained quaternary amidinium salts against Escherichia coli and Staphylococcus aureus bacterial strains and Candida albicans yeast was investigated, and the impact of the used protecting groups and the sugar configuration on the antimicrobial activity was analyzed. Some of the novel sugar quaternary ammonium compounds with lipophilic aromatic groups (benzyl and 2-napthylmethyl) showed particularly good antifungal and antibacterial activity. LA - English DB - MTMT ER - TY - JOUR AU - Demeter, Fruzsina AU - Bényei, Attila Csaba AU - Borbás, Anikó AU - Herczeg, Mihály TI - Synthesis of the Three Most Expensive l-Hexose Thioglycosides from d-Glucose JF - SYNTHESIS-STUTTGART J2 - SYNTHESIS-STUTTGART VL - 55 PY - 2023 IS - 7 SP - 1087 EP - 1111 PG - 25 SN - 0039-7881 DO - 10.1055/s-0042-1751394 UR - https://m2.mtmt.hu/api/publication/33574039 ID - 33574039 N1 - Published online: 21 December 2022 AB - The biologically important l-hexoses, which are less widespread than d-hexoses, cannot be obtained from natural sources or can only be extracted very costly. Due to the complexity of their synthesis, their commercially available derivatives (which are sold mostly in free form) are also very expensive, which is further exacerbated by the current rapid rise in prices. In the present work, starting from the cheapest d-hexose, d-glucose, using inexpensive and readily available chemicals, a reaction pathway was developed in which the three most expensive l-hexoses (l-idose, l-altrose, and l-talose) were successfully prepared in orthogonally protected thioglycoside form, ready for glycosylation. The l-ido and l-talo derivatives were synthesized by C-5 epimerization of the corresponding 5,6-unsaturated thioglycosides. From the l-ido derivatives, the orthogonally protected thioglycosides of l-altrose were then prepared by C-4 epimerization. Different approaches to the preparation of the key intermediates, 5,6-unsaturated thioglycoside derivatives, were systematically investigated in the presence of various protecting groups (ether and ester) and using commercially available reagents. LA - English DB - MTMT ER - TY - JOUR AU - Herczeg, Mihály AU - Demeter, Fruzsina AU - Lisztes, Erika AU - Racskó, Márk AU - Tóth, Balázs István AU - Timári, István AU - Bereczky, Zsuzsanna AU - E Kövér, Katalin AU - Borbás, Anikó TI - Synthesis of a Heparinoid Pentasaccharide Containing L-Guluronic Acid Instead of L-Iduronic Acid with Preserved Anticoagulant Activity JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 87 PY - 2022 IS - 23 SP - 15830 EP - 15836 PG - 7 SN - 0022-3263 DO - 10.1021/acs.joc.2c01928 UR - https://m2.mtmt.hu/api/publication/33332835 ID - 33332835 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [K 132870, K 139293, NN 128368, FK 137924, PD 134791, PD 135034]; Premium Postdoctoral Program of HAS [PPD 461038]; EU; European Regional Development Fund [GINOP-2.3.4-15-2020-00008, GINOP-2.3.3-15-2016-00004]; Janos Bolyai Scholarship of the Hungarian Academy of Science; Debrecen Venture Catapult [EFOP-3.6.1-16-2016-0022]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00372/20/7]; New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [UNKP-22-5-DE-424] Funding text: The research was supported by the National Research, Development and Innovation Office of Hungary (K 132870, A.B.; K 139293, Z.B.; NN 128368, K.E.K.; FK 137924, M.H.; PD 134791, E.L., and PD 135034, I.T.), Premium Postdoctoral Program of HAS (PPD 461038, M.H.), and the EU and co-financed by the European Regional Development Fund under the project GINOP-2.3.4-15-2020-00008 and GINOP-2.3.3-15-2016-00004. B.I.T. was supported by the Janos Bolyai Scholarship of the Hungarian Academy of Science, and M.R. was supported by EFOP-3.6.1-16-2016-0022 "Debrecen Venture Catapult." I.T. acknowledges the support of the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00372/20/7) and the UNKP-22-5-DE-424 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund . The authors would like to thank Marta Bodza and EEva Molnar for their technical assistance. AB - L-Iduronic acid is a key constituent of heparin and heparan sulfate polysaccharides due to its unique conformational plasticity, which facilitates the binding of polysaccharides to proteins. At the same time, this is the synthetically most challenging unit of heparinoid oligosaccharides; therefore, there is a high demand for its replacement with a more easily accessible sugar unit. In the case of idraparinux, an excellent anticoagulant heparinoid pentasaccharide, we demonstrated that L-iduronic acid can be replaced by an easier-to-produce L-sugar while maintaining its essential biological activity. From the inexpensive D-mannose, through a highly functionalized phenylthio mannoside, the L-gulose donor was prepared by C-5 epimerization in 10 steps with excellent yield. This unit was incorporated into the pentasaccharide by alpha-selective glycosylation and oxidized to L-guluronic acid. The complete synthesis required only 36 steps, with 21 steps for the longest linear route. The guluronate containing pentasaccharide inhibited coagulation factor Xa by 50% relative to the parent compound, representing an excellent anticoagulant activity. To the best of our knowledge, this is the first biologically active heparinoid anticoagulant which contains a different sugar unit instead of L-iduronic acid. LA - English DB - MTMT ER - TY - JOUR AU - Demeter, Fruzsina AU - Bakai-Bereczki, Ilona AU - Borbás, Anikó AU - Herczeg, Mihály TI - Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 11 PG - 35 SN - 1420-3049 DO - 10.3390/molecules27113422 UR - https://m2.mtmt.hu/api/publication/32859682 ID - 32859682 AB - l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21-23%) and l-galactose derivatives in 12 steps (total yields: 6-8%) starting from d-mannose. LA - English DB - MTMT ER - TY - CHAP AU - Magdolna, Csávás AU - Herczeg, Mihály AU - István, Bajza AU - Borbás, Anikó ED - Joseph, J Barchi TI - Protecting Group Manipulations in Carbohydrate Synthesis T2 - Comprehensive Glycoscience PB - Elsevier CY - Amsterdam SN - 0128222441 PY - 2021 SP - 464 EP - 524 PG - 61 DO - 10.1016/B978-0-12-819475-1.00087-0 UR - https://m2.mtmt.hu/api/publication/32465340 ID - 32465340 N1 - Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Hungary Research Group for Oligosaccharide Chemistry of HAS, University of Debrecen, Debrecen, Hungary Glycoptim Ltd., Debrecen, Hungary Cited By :3 Export Date: 23 February 2023 Correspondence Address: Csávás, M.; Department of Pharmaceutical Chemistry, Hungary LA - English DB - MTMT ER -