TY - JOUR AU - Kovács, Hilda AU - Jakusch, Tamás AU - May, Nóra Veronika AU - Tóth, Szilárd AU - Szakács, Gergely AU - Enyedy, Éva Anna TI - Complex formation of ML324, the histone demethylase inhibitor, with essential metal ions: Relationship between solution chemistry and anticancer activity JF - JOURNAL OF INORGANIC BIOCHEMISTRY J2 - J INORG BIOCHEM VL - 255 PY - 2024 PG - 12 SN - 0162-0134 DO - 10.1016/j.jinorgbio.2024.112540 UR - https://m2.mtmt.hu/api/publication/34761990 ID - 34761990 LA - English DB - MTMT ER - TY - JOUR AU - Orgován, Zoltán AU - Péczka, Nikolett AU - Petri, László AU - Ábrányi-Balogh, Péter AU - Randelovic, Ivan AU - Tóth, Szilárd AU - Szakács, Gergely AU - Nyíri, Kinga AU - Vértessy, Beáta (Grolmuszné) AU - Pálfy, Gyula AU - Vida, István AU - Perczel, András AU - Tóvári, József AU - Keserű, György Miklós TI - Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 250 PY - 2023 PG - 7 SN - 0223-5234 DO - 10.1016/j.ejmech.2023.115212 UR - https://m2.mtmt.hu/api/publication/33647485 ID - 33647485 N1 - Medicinal Chemistry Research Group, Research Centre for Natural Sciences, and National Drug Discovery and Development Laboratory, Budapest, Hungary Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Budapest, Hungary KINETO Lab Ltd, Budapest, Hungary Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Hungary Laboratory of Structural Chemistry and Biology, Eötvös Loránd University, Budapest, Hungary MTA-ELTE Protein Modelling Research Group, Eötvös Loránd University, Budapest, Hungary Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary CODEN: EJMCA Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, 2 Magyar tudósok kӧrútja, Hungary; email: keseru.gyorgy@ttk.hu AB - G12C mutant KRas is considered druggable by allele-specific covalent inhibitors due to the nucleophilic character of the oncogenic mutant cysteine at position 12. Discovery of these inhibitors requires the optimization of both covalent and noncovalent interactions. Here, we report covalent fragment screening of our electrophilic fragment library of diverse non-covalent scaffolds equipped with 40 different electrophilic functionalities to identify fragments as suitable starting points targeting Cys12. Screening the library against KRasG12C using Ellman's free thiol assay, followed by protein NMR and cell viability assays, resulted in two potential inhibitor chemotypes. Characterization of these scaffolds in in vitro cellular- and in vivo xenograft models revealed them as promising starting points for covalent drug discovery programs. LA - English DB - MTMT ER - TY - JOUR AU - Pivarcsik, Tamás AU - Pósa, Vivien AU - Kovács, Hilda AU - May, Nóra Veronika AU - Spengler, Gabriella AU - Pósa, Szonja P. AU - Tóth, Szilárd AU - Nezafat Yazdi, Zeinab AU - Laczka, Csilla AU - Ugrai, Imre AU - Szatmári, István AU - Szakács, Gergely AU - Enyedy, Éva Anna TI - Metal Complexes of a 5-Nitro-8-Hydroxyquinoline-Proline Hybrid with Enhanced Water Solubility Targeting Multidrug Resistant Cancer Cells JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 1 PG - 27 SN - 1661-6596 DO - 10.3390/ijms24010593 UR - https://m2.mtmt.hu/api/publication/33532438 ID - 33532438 N1 - MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary Centre for Structural Science, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary Department of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, Szeged, H-6725, Hungary Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary National Laboratory for Drug Research and Development, Magyar Tudósok krt. 2, Budapest, H-1117, Hungary Institute of Pharmaceutical Chemistry and Stereochemistry Research Group, Eötvös Loránd Research Network, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria Cited By :2 Export Date: 20 September 2023 Correspondence Address: Enyedy, É.A.; MTA-SZTE Lendület Functional Metal Complexes Research Group, Dóm tér 7, Hungary; email: enyedy@chem.u-szeged.hu Chemicals/CAS: ferric ion, 20074-52-6; ferrous ion, 15438-31-0; nitroxoline, 4008-48-4; zinc ion, 23713-49-7; proline, 147-85-3, 7005-20-1; ruthenium, 7440-18-8; water, 7732-18-5; Antineoplastic Agents; Coordination Complexes; Ferric Compounds; Ferrous Compounds; Ions; Ligands; nitroxoline; Organometallic Compounds; Proline; Ruthenium; Water Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, FK128751, K138518, LP2019-6/2019, RRF-2.3.1-21-2022-00015, TKP-2021-EGA-32 Funding text 1: This work was supported by National Research, Development and Innovation Fund (Hungary) through projects TKP-2021-EGA-32, FK128751, RRF-2.3.1-21-2022-00015 and K138518. The support of the “Lendület” Programme (ELKH, LP2019-6/2019) is also acknowledged (É.A.E.). AB - Multidrug resistance (MDR) in cancer is one of the major obstacles of chemotherapy. We have recently identified a series of 8-hydroxyquinoline Mannich base derivatives with MDR-selective toxicity, however with limited solubility. In this work, a novel 5-nitro-8-hydroxyquinoline-proline hybrid and its Rh(η5-C5Me5) and Ru(η6-p-cymene) complexes with excellent aqueous solubility were developed, characterized, and tested against sensitive and MDR cells. Complex formation of the ligand with essential metal ions was also investigated using UV-visible, circular dichroism, 1H NMR (Zn(II)), and electron paramagnetic resonance (Cu(II)) spectroscopic methods. Formation of mono and bis complexes was found in all cases with versatile coordination modes, while tris complexes were also formed with Fe(II) and Fe(III) ions, revealing the metal binding affinity of the ligand at pH 7.4: Cu(II) > Zn(II) > Fe(II) > Fe(III). The ligand and its Rh(III) complex displayed enhanced cytotoxicity against the resistant MES-SA/Dx5 and Colo320 human cancer cell lines compared to their chemosensitive counterparts. Both organometallic complexes possess high stability in solution, however the Ru(II) complex has lower chloride ion affinity and slower ligand exchange processes, along with the readiness to lose the arene ring that is likely connected to its inactivity. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Petra Regina AU - Dinnyési, Emőke AU - Tóth, Szilárd AU - Szakács, Gergely AU - Keglevich, György TI - Optimized Synthesis and Cytotoxic Activity of α Aminophosphonates against a Multidrug Resistant Uterine Sarcoma Cell Line JF - LETTERS IN DRUG DESIGN AND DISCOVERY J2 - LETT DRUG DES DISCOV VL - 20 PY - 2023 IS - 3 SP - 365 EP - 371 PG - 7 SN - 1570-1808 DO - 10.2174/1570180819666220609104427 UR - https://m2.mtmt.hu/api/publication/33083436 ID - 33083436 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [K134318]; [HunPro-tEx 2018-1.2.1-NKP-2018-00005] Funding text: This project was supported by the National Research, Development and Innovation Office (K134318) and HunPro-tEx 2018-1.2.1-NKP-2018-00005. LA - English DB - MTMT ER - TY - JOUR AU - Pósa, Szonja Polett AU - Dargó, Gyula AU - Nagy, Sándor AU - Kisszékelyi, Péter AU - Garádi, Zsófia AU - Hámori, Lilla AU - Szakács, Gergely AU - Kupai, József AU - Tóth, Szilárd TI - Cytotoxicity of cinchona alkaloid organocatalysts against MES-SA and MES-SA/Dx5 multidrug-resistant uterine sarcoma cell lines JF - BIOORGANIC & MEDICINAL CHEMISTRY J2 - BIOORGAN MED CHEM VL - 67 PY - 2022 PG - 7 SN - 0968-0896 DO - 10.1016/j.bmc.2022.116855 UR - https://m2.mtmt.hu/api/publication/32848262 ID - 32848262 N1 - Funding Agency and Grant Number: New National Excellence Program of the Ministry of Human Capacities ? [NKP-20-5-BME-322]; Ja?nos Bolyai Research Scholarship of the Hungarian Academy of Science [FK138037]; National Research, Development, and Innovation Office [2019-1.3.1-KK-2019-00007, 0983-20 405]; Richter Gedeon Excellence PhD Scholarship of Gedeon Richter Talentum Foundation (Gedeon Richter Plc.) - National Research, Devel-opment and Innovation Fund of Hungary; Hungarian Academy of Sciences Funding text: This research was funded by the New National Excellence Program of the Ministry of Human Capacities ?NKP-20-5-BME-322 (J.K.) , and the Ja?nos Bolyai Research Scholarship of the Hungarian Academy of Science (J.K.) . It was also supported by the National Research, Development, and Innovation Office (grant number FK138037) , the Servier-Beregi PhD Research Fellowship (S.N.) , and the Richter Gedeon Excellence PhD Scholarship of Gedeon Richter Talentum Foundation (Gedeon Richter Plc.) (G.D.) . Moreover, it was funded by the National Research, Devel-opment and Innovation Fund of Hungary (2019-1.3.1-KK-2019-00007) , and by a grant called KEP (Kiva?lo?sa?gi Egy?ttmu?ko?de?si Program; 0983-20 405) of the Hungarian Academy of Sciences and Eo?tvo?s Lora?nd Research Network (ELKH) (G.S.) LA - English DB - MTMT ER - TY - JOUR AU - Pape, Veronika AU - Palkó, Roberta AU - Tóth, Szilárd AU - Szabó, Miklós J. AU - Sessler, Judit AU - Dormán, György AU - Enyedy, Éva Anna AU - Soós, Tibor AU - Szatmári, István AU - Szakács, Gergely TI - Structure–Activity Relationships of 8-Hydroxyquinoline-Derived Mannich Bases with Tertiary Amines Targeting Multidrug-Resistant Cancer JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 65 PY - 2022 IS - 11 SP - 7729 EP - 7745 PG - 17 SN - 0022-2623 DO - 10.1021/acs.jmedchem.2c00076 UR - https://m2.mtmt.hu/api/publication/32843044 ID - 32843044 LA - English DB - MTMT ER - TY - JOUR AU - Varga, Petra Regina AU - Belovics, Alexandra AU - Bagi, Péter AU - Tóth, Szilárd AU - Szakács, Gergely AU - Bősze, Szilvia AU - Szabó, Rita AU - Drahos, László AU - Keglevich, György TI - Efficient Synthesis of Acylated, Dialkyl α-Hydroxy-Benzylphosphonates and Their Anticancer Activity JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 7 SN - 1420-3049 DO - 10.3390/molecules27072067 UR - https://m2.mtmt.hu/api/publication/32788926 ID - 32788926 N1 - Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, 1521, Hungary Research Centre for Natural Sciences, Institute of Enzymology, Budapest, 1117, Hungary Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, Vienna, A-1090, Austria Eötvös Loránd Research Network (ELKH), Research Group of Peptide Chemistry, Eötvös Loránd University, Budapest, 1117, Hungary Research Centre for Natural Sciences, MS Proteomics Research Group, Budapest, 1117, Hungary Export Date: 21 April 2022 CODEN: MOLEF Correspondence Address: Keglevich, G.; Department of Organic Chemistry and Technology, Hungary; email: keglevich.gyorgy@vbk.bme.hu LA - English DB - MTMT ER - TY - JOUR AU - Cserepes, Tamás Mihály AU - Türk, Dóra AU - Tóth, Szilárd AU - Pape, Veronika AU - Gaál, Anikó AU - Gera, Melinda AU - Szabó, Judit Eszter AU - Kucsma, Nóra AU - Várady, György AU - Vértessy, Beáta G. AU - Streli, Christina AU - Szabó, Pál Tamás AU - Tóvári, József AU - Szoboszlai, Norbert AU - Szakács, Gergely TI - Multidrogrezisztens tumorok célzott elpusztítása a P-glikoproteint expresszáló sejtek szelektív vasdepléciójával JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 65 PY - 2021 IS - 5 Suppl. 1 SP - 15 EP - 15 PG - 1 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/32540679 ID - 32540679 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Sonja, Hager AU - Pape, Veronika AU - Pósa, Vivien AU - Bianca, Montsch AU - Lukas, Uhlik AU - Szakács, Gergely AU - Tóth, Szilárd AU - Nikolett, Jabronka AU - Bernhard, K. Keppler AU - Walter, Berger AU - Christian, R. Kowol AU - Enyedy, Éva Anna AU - Petra, Heffeter TI - Improved activity and paraptosis-induction of anticancer thiosemicarbazones requires high copper(II) complex stability and slow reduction kinetics JF - CANCER RESEARCH J2 - CANCER RES VL - 80 PY - 2020 IS - 16 SP - 1939 EP - 1939 PG - 1 SN - 0008-5472 DO - 10.1158/1538-7445.AM2020-1939 UR - https://m2.mtmt.hu/api/publication/31449756 ID - 31449756 LA - English DB - MTMT ER - TY - JOUR AU - Sonja, Hager AU - Pape, Veronika AU - Pósa, Vivien AU - Bianca, Montsch AU - Lukas, Uhlik AU - Szakács, Gergely AU - Tóth, Szilárd AU - Nikolett, Jabronka AU - Bernhard, K. Keppler AU - Christian, R. Kowol AU - Enyedy, Éva Anna AU - Petra, Heffeter TI - High copper complex stability and slow reduction kinetics as key parameters for improved activity, paraptosis induction and impact on drug-resistant cells of anticancer thiosemicarbazones JF - ANTIOXIDANTS & REDOX SIGNALING J2 - ANTIOXID REDOX SIGNAL VL - 33 PY - 2020 IS - 6 SP - 395 EP - 414 PG - 10 SN - 1523-0864 DO - 10.1089/ars.2019.7854 UR - https://m2.mtmt.hu/api/publication/31305929 ID - 31305929 N1 - Institute of Cancer Research, Medical University of Vienna, Vienna, Austria Research Cluster 'Translational Cancer Therapy Research, Vienna, Austria Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary Department of Physiology, Semmelweis University, Budapest, Hungary Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Szeged, Hungary Faculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Vienna, Austria Cited By :25 Export Date: 18 September 2023 CODEN: ARSIF Correspondence Address: Enyedy, E.A.; Department of Inorganic and Analytical Chemistry, Domter 7, Hungary; email: enyedy@chem.u-szeged.hu Correspondence Address: Heffeter, P.; Institute of Cancer Research, Borschkeg. 8a, Austria; email: petra.heffeter@meduniwien.ac.at Chemicals/CAS: protein disulfide isomerase, 37318-49-3; superoxide, 11062-77-4; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; copper, 15158-11-9, 7440-50-8; Antineoplastic Agents; Antioxidants; Copper; Thiosemicarbazones Funding details: European Molecular Biology Organization, EMBO, ASTF335-2016 Funding details: Austrian Science Fund, FWF, P31923 Funding details: National Research, Development and Innovation Office, FK 124240, TUDFO/47138-1/2019-ITM Funding text 1: This work was supported by the National Research, Development and Innovation Office-NKFI through project FK 124240 and FIKP program TUDFO/47138-1/2019-ITM. Furthermore, this work was in part funded by the Austrian Science Fund (FWF) grant number P31923 (to C.R. Kowol and P. Heffeter) as well as by the bilateral program Scientific and Technological Cooperation of the OeAD. Part of the data was generated in course of the research exchange program Aktion ‘‘Österreich-Ungarn’’ as well as in a short-term fellowship of the European Molecular Biology Organization (EMBO, grant ASTF335-2016) both to P. Heffeter. S. Hager is a recipient of a DOC Fellowship of the Austrian Academy of Sciences. The funding sources had no involvement in the collection, analysis, and interpretation of data as well as in the decision to submit the article for publication. LA - English DB - MTMT ER -