TY - JOUR AU - Háznagy, Márton Benedek AU - Csámpai, Antal AU - Ugrai, Imre AU - Barnabás, Molnár AU - Matti, Haukka AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Catalytical Application of Perillaldehyde-Based 3-Amino-1,2-diol Regioisomers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 25 SN - 1661-6596 DO - 10.3390/ijms25084325 UR - https://m2.mtmt.hu/api/publication/34791082 ID - 34791082 AB - A library of regioisomeric monoterpene-based aminodiols was synthesised and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The synthesis of the first type of aminodiols was achieved starting from (−)-8,9-dihydroperillaldehyde via reductive amination, followed by Boc protection and dihydroxylation with the OsO4/NMO system. Separation of formed stereoisomers resulted in a library of aminodiol diastereoisomers. The library of regioisomeric analogues was obtained starting from (−)-8,9-dihydroperillic alcohol, which was transformed into a mixture of allylic trichloroacetamides via Overman rearrangement. Changing the protecting group to a Boc function, the protected enamines were subjected to dihydroxylation with the OsO4/NMO system, leading to a 71:16:13 mixture of diastereoisomers, which were separated, affording the three isomers in isolated form. The obtained primary aminodiols were transformed into secondary derivatives. The regioselectivity of the ring closure of the N-benzyl-substituted aminodiols with formaldehyde was also investigated, resulting in 1,3-oxazines in an exclusive manner. To explain the stability difference between diastereoisomeric 1,3-oxazines, a series of comparative theoretical modelling studies was carried out. The obtained potential catalysts were applied in the reaction of aromatic aldehydes and diethylzinc with moderate to good enantioselectivities (up to 94% ee), whereas the opposite chiral selectivity was observed between secondary aminodiols and their ring-closed 1,3-oxazine analogues. LA - English DB - MTMT ER - TY - JOUR AU - Ozsvár, Dániel AU - Bózsity-Faragó, Noémi AU - Zupkó, István AU - Szakonyi, Zsolt TI - Synthesis and Study of the Structure–Activity Relationship of Antiproliferative N-Substituted Isosteviol-Based 1,3-Aminoalcohols JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 17 PY - 2024 IS - 2 PG - 18 SN - 1424-8247 DO - 10.3390/ph17020262 UR - https://m2.mtmt.hu/api/publication/34666945 ID - 34666945 AB - Starting from isosteviol, a series of diterpenoid 1,3-aminoalcohol derivatives were prepared via stereoselective transformations. The acid-catalysed hydrolysis and rearrangement of natural stevioside produced isosteviol, which was transformed into the key intermediate methyl ester. In the next step, an 1,3-aminoalcohol library was prepared by the reductive amination of the intermediate 3-hydroxyaldehyde obtained from isosteviol in a two-step synthesis. To study the effect of the carboxylate ester function at position 4, the free carboxylic acid, benzyl ester and acryloyl ester analogues were prepared as elongated derivatives in comparison with our earlier results in this field. The antiproliferative activity of compounds against human tumour cell lines (A2780, HeLa, MCF-7 and MDA-MB-231) was investigated. In our preliminary study, the 1,3-aminoalcohol function with N-benzyl or (1H-imidazol-1-yl)-propyl substitution and benzyl ester moiety seemed essential for the reliable antiproliferative activity. The results obtained could be a good starting point to further functionalisation towards more efficient antiproliferative diterpenes. LA - English DB - MTMT ER - TY - JOUR AU - Khdar, Zein Alabdeen AU - Le Minh, Tam AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Szakonyi, Zsolt TI - Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohols regioisomers JF - RSC MEDICINAL CHEMISTRY J2 - RSC MED CHEM VL - 15 PY - 2024 IS - 3 SP - 874 EP - 887 PG - 14 SN - 2632-8682 DO - 10.1039/D3MD00665D UR - https://m2.mtmt.hu/api/publication/34577084 ID - 34577084 AB - A new library of allo -gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo -gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl... LA - English DB - MTMT ER - TY - JOUR AU - Németi, Gábor AU - Berkecz, Róbert AU - Le Minh, Tam AU - Szakonyi, Zsolt AU - Péter, Antal AU - Ilisz, István TI - High-performance liquid chromatographic enantioseparation of azole analogs of monoterpene lactones and amides focusing on the separation characteristics of polysaccharide-based chiral stationary phases JF - JOURNAL OF CHROMATOGRAPHY A J2 - J CHROMATOGR A VL - 1717 PY - 2024 PG - 9 SN - 0021-9673 DO - 10.1016/j.chroma.2024.464660 UR - https://m2.mtmt.hu/api/publication/34535772 ID - 34535772 N1 - Institute of Pharmaceutical Analysis, Interdisciplinary Excellence Centre, University of Szeged, Somogyi u. 4, Szeged, H-6720, Hungary Institute of Pharmaceutical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary Export Date: 5 February 2024 CODEN: JCRAE Correspondence Address: Ilisz, I.; Institute of Pharmaceutical Analysis, Somogyi u. 4, Hungary; email: ilisz.istvan@szte.hu Funding details: 6752 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Innovációs és Technológiai Minisztérium Funding details: National Research, Development and Innovation Office, K137607, TKP2021-EGA-32 Funding text 1: This work was supported by the National Research, Development and Innovation Office-NKFIA through project K137607. Project no. TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. This work was supported by the ÚNKP-21-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. The publication was funded by the University of Szeged Open Access Fund (No. 6752). LA - English DB - MTMT ER - TY - JOUR AU - Bai, Dorottya AU - Schelz, Zsuzsanna AU - Boncz, Mária Fanni AU - Zupkó, István AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 24 PG - 22 SN - 1420-3049 DO - 10.3390/molecules28247962 UR - https://m2.mtmt.hu/api/publication/34417276 ID - 34417276 N1 - Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Export Date: 8 January 2024 CODEN: MOLEF Correspondence Address: Szakonyi, Z.; Interdisciplinary Excellence Center, Eötvös utca 6, Hungary; email: schelz.zsuzsanna@szte.hu Chemicals/CAS: steviol, 471-80-7; Amino Alcohols; steviol Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI, K138871, TKP2021-EGA-32 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: We are grateful for financial support from the Hungarian Research Foundation (NKFI K138871). Project no. TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. AB - A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method. LA - English DB - MTMT ER - TY - JOUR AU - Szakonyi, Zsolt TI - Stájer Géza (1936-2015) JF - MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-) J2 - MAGY KÉM FOLY KÉM KÖZL VL - 129 PY - 2023 IS - 2 SP - 46 EP - 49 PG - 4 SN - 1418-9933 DO - 10.24100/MKF.2023.02.46 UR - https://m2.mtmt.hu/api/publication/34353508 ID - 34353508 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Nagy, Viktória AU - Mounir, Raji AU - Szebeni, Gábor AU - Szakonyi, Zsolt AU - Gémes, Nikolett AU - Minorics, Renáta AU - Germán, Péter AU - Zupkó, István TI - Investigation of Anticancer Properties of Monoterpene-Aminopyrimidine Hybrids on A2780 Ovarian Cancer Cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 13 PG - 17 SN - 1661-6596 DO - 10.3390/ijms241310581 UR - https://m2.mtmt.hu/api/publication/34034428 ID - 34034428 N1 - Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, H-6720, Hungary Institute of Pharmaceutical Chemistry, University of Szeged, Szeged, H-6720, Hungary Laboratory of Functional Genomics, Eötvös Loránd Research Network Biological Research Centre, Institute of Genetics, Szeged, H-6726, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, H-6720, Hungary Export Date: 24 July 2023 Correspondence Address: Zupkó, I.; Institute of Pharmacodynamics and Biopharmacy, Hungary; email: zupko.istvan@szte.hu Funding details: Magyar Tudományos Akadémia, MTA, BO/00582/22/8, TKP2021-EGA-32 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, 142877 FK22, 2020-1.1.6-JÖVŐ-2021-00003, K 143690 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: This research was funded by the Hungarian Research Foundation (NKFI), grant numbers K 143690, 142877 FK22, and 2020-1.1.6-JÖVŐ-2021-00003, as well as by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (G.J.S.). TKP2021-EGA-32 was implemented with support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. AB - The present study aimed to characterize the antiproliferative and antimetastatic properties of two recently synthesized monoterpene-aminopyrimidine hybrids (1 and 2) on A2780 ovary cancer cells. Both agents exerted a more pronounced cell growth inhibitory action than the reference agent cisplatin, as determined by the MTT assay. Tumor selectivity was assessed using non-cancerous fibroblast cells. Hybrids 1 and 2 induced changes in cell morphology and membrane integrity in A2780 cells, as evidenced by Hoechst 33258–propidium iodide fluorescent staining. Cell cycle analysis by flow cytometry revealed substantial changes in the distribution of A2780 ovarian cancer cells, with an increased rate in the subG1 and G2/M phases, at the expense of the G1 cell population. Moreover, the tested molecules accelerated tubulin polymerization in a cell-free in vitro system. The antimetastatic properties of both tested compounds were investigated by wound healing and Boyden chamber assays after 24 and 48 h of incubation. Treatment with 1 and 2 resulted in time- and concentration-dependent inhibition of migration and invasion of A2780 cancer cells. These results support that the tested agents may be worth of further investigation as promising anticancer drug candidates. LA - English DB - MTMT ER - TY - CONF AU - Kozma-Bognárné Hamari, Zsuzsanna AU - Eszter, Bokor AU - Ámon, Judit AU - Varga, Mónika AU - Szekeres, András AU - Hegedüs, Zsófia AU - Tamás, Jakusch AU - Szakonyi, Zsolt AU - Flipphi, Michel Johannes Anthonie AU - Vágvölgyi, Csaba AU - Gácser, Attila AU - Claudio, Scazzocchio TI - NICOTINIC ACID CATABOLISM IN ASPERGILLUS NIDULANS: AN EXAMPLE OF CONVERGENT EVOLUTION T2 - 16th European Conference on Fungal Genetics: Programme & Abstracts PB - Universität Innsbruck C1 - Innsbruck PY - 2023 SP - 767 EP - 768 PG - 2 UR - https://m2.mtmt.hu/api/publication/33693549 ID - 33693549 AB - Nicotinic acid (niacin) is a precursor of NAD and NADP and thus an essential metabolite. Its degradation has been previously described only in bacteria. We describe, for the first time, a complete eukaryotic pathway of nico- tinic acid (NA) catabolism. The genes are organised in three co-regu- lated gene clusters, which encode eight enzymes, two transporters and the pathway specific transcription factor. The pathway is conserved; and its variable organisation in the Pezizomycotina illustrates cluster evolution and horizontal gene transfer. Reverse genetics was coupled with state-of-the-art chemical charac- terisation of each intermediate. The first step, the conversion of NA to 6-hydroxynicotinic acid (6-NA) is common to prokaryotic and eukary- otic pathways, even if catalysed by independently evolved enzymes. While two downstream metabolites, 2,5-dihydroxypyridine and 2,3,6-tri- hydroxypyridine, are common to various prokaryotic routes, other steps and metabolites are unprecedented: 3-hydroxypiperidine-2,6-dione and 5,6-dihydroxypiperidine-2-one intermediate metabolites have not been identified previously in any organism, the latter being a completely nov- el chemical compound. Furthermore, the hydrolytic N-C ring opening results in α-hydroxyglutaramate, a compound not detected in analo- gous prokaryotic pathways. Remarkably, the physiological inducer of the whole pathway is a near-terminal intermediate metabolite: 5,6-di- hydroxypiperidine-2-one. While most steps are cytosolic, two steps take place in the peroxi- somes. 6-NA monooxygenase (HxnX) enters peroxisomes through a canonical PTS-1 signal, while HxnW, a polyol dehydrogenase, is co-transported by piggybacking HxnX. The genomic organisation and phylogeny of the pathway cognate genes and proteins, showed that this catabolic pathway is of fungal (Ascomycota) origin and thus it exemplifies convergent evolution of catabolic pathways between fungi and bacteria, where at least four different pathways occur. LA - English DB - MTMT ER - TY - JOUR AU - Bai, Dorottya AU - Schelz, Zsuzsanna AU - Erdős, Dóra AU - Kis, Anna K. AU - Nagy, Viktória AU - Zupkó, István AU - Balogh, György Tibor AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 2 PG - 18 SN - 1661-6596 DO - 10.3390/ijms24021121 UR - https://m2.mtmt.hu/api/publication/33547781 ID - 33547781 N1 - Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Muegyetem rkp. 3, Budapest, H-1111, Hungary Correspondence Address: Szakonyi, Z.; Interdisciplinary Excellence Center, Eötvös utca 6, Hungary; email: szakonyi.zsolt@szte.hu AB - A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an N,O-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic N-substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements. LA - English DB - MTMT ER - TY - CHAP AU - Nagy, Viktória AU - Mounir, Raji AU - Szakonyi, Zsolt AU - Gábor, J. Szebeni AU - Zupkó, István ED - Muszynska, Bozena TI - Pharmacological investigation of a newly synthesized monoterpene-based 2,4-diaminopyrimidine type derivatives lines in vitro T2 - Natural vs. Artificial Networks: The Usefulness of the Concept in Health, Life, and Technical Sciences PB - Zakład Optymalizacji Zawodowej Ośrodek Umea Shinoda-Kuracejo CY - Martin CY - Krakow CY - Szeged SN - 9788395955457 PY - 2022 SP - 85 EP - 86 PG - 2 UR - https://m2.mtmt.hu/api/publication/33643161 ID - 33643161 AB - According to estimates from the World Health Organization (WHO), cancer ranks as one of the major health burdens and a leading cause of mortality globally. Gynecologic cancers (breast, uterus, cervix, and ovaries) are found among the 10 most frequently diagnosed cancer types. Natural products including terpenes are one of the most investigated group of compounds in lead-finding studies. Several studies have revealed that monoterpenes may prevent the carcinogenesis process and exert growthinhibiting action against cancer cells. To determine the antiproliferative activity of a newly synthesized set of monoterpene-based 2,4-diaminopyrimidine type derivatives against gynecological cancer cell lines. The mechanism of the most effective analogues was additionally tested to describe their mechanism of action. The growth-inhibitory effects of the tested compounds were determined by MTT assay on a cell line panel (Hela, Siha, MDA-MB-231, and MCF-7, A2780, and NIH/3T3 fibroblast to characterize the cancer selectivity). To identify the changes in the cell cycle phase distribution of the treated cells, cell cycle analysis was performed. To distinguish apoptotic and necrotic cells by their nuclear morphology and membrane integrity, fluorescent staining was applied. Two out of 20 monoterpene derivatives exhibited promising antiproliferative action with IC50 values below 10 μM. These analogues elicited substantial changes in the cell cycle distribution of A2780 ovarian cancer cells with increased number of cells in SubG1 and G2/M phases on the expense of G1 population. The proapoptotic potential of these agents were confirmed by propidium-Hoechst 33258 staining. Our results suggest that the new monoterpene compounds may be regarded as promising candidates in the development of new anticancer agents, against ovarian cancer cell lines. LA - English DB - MTMT ER -