TY - JOUR AU - Hlogyik, Tamás AU - Laczkó-Rigó, Réka AU - Bakos, Éva AU - Poór, Miklós AU - Kele, Zoltán AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Synthesis and in vitro photodynamic activity of aza-BODIPY-based photosensitizers JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 21 PY - 2023 IS - 29 SP - 6018 EP - 6027 PG - 10 SN - 1477-0520 DO - 10.1039/d3ob00699a UR - https://m2.mtmt.hu/api/publication/34067941 ID - 34067941 N1 - * Megosztott szerzőség AB - Aza-BODIPY dyes have recently come to attention owing to their excellent chemical and photophysical properties. In particular, their absorption and emission maxima can efficiently be shifted to the red or even to the NIR spectral region. On this basis, aza-BODIPY derivatives are widely investigated as fluorescent probes or phototherapeutic agents. Here we report the synthesis of a set of novel aza-BODIPY derivatives as potential photosensitizers for use in photodynamic therapy. Triazolyl derivatives were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition as the key step. In vitro photodynamic activities of the newly synthesized compounds were evaluated on the A431 human epidermoid carcinoma cell line. Structural differences influenced the light-induced toxicity of the test compounds markedly. Compared to the initial tetraphenyl aza-BODIPY derivative, the compound bearing two hydrophilic triethylene glycol side chains showed substantial, more than 250-fold, photodynamic activity with no dark toxicity. Our newly synthesized aza-BODIPY derivative, acting in the nanomolar range, might serve as a promising candidate for the design of more active and selective photosensitizers. LA - English DB - MTMT ER - TY - THES AU - Laczkó-Rigó, Réka TI - OATP2B1, as a possible target of hormone dependent cancer treatment PB - Eötvös Loránd Tudományegyetem (ELTE) PY - 2022 SP - 119 DO - 10.15476/ELTE.2021.150 UR - https://m2.mtmt.hu/api/publication/33628978 ID - 33628978 LA - English DB - MTMT ER - TY - JOUR AU - Laczkó-Rigó, Réka AU - Bakos, Éva AU - Jójárt, Rebeka AU - Tömböly, Csaba AU - Mernyák, Erzsébet AU - Laczka, Csilla TI - Selective antiproliferative effect of C-2 halogenated 13α-estrones on cells expressing Organic anion-transporting polypeptide 2B1 (OATP2B1) JF - TOXICOLOGY AND APPLIED PHARMACOLOGY J2 - TOXICOL APPL PHARM VL - 429 PY - 2021 PG - 9 SN - 0041-008X DO - 10.1016/j.taap.2021.115704 UR - https://m2.mtmt.hu/api/publication/32178981 ID - 32178981 AB - Organic anion-transporting polypeptide 2B1 (OATP2B1) is a multispecific transporter mediating the cellular uptake of steroids and numerous drugs. OATP2B1 is abundantly expressed in the intestine and is also present in various tumors. Increased steroid hormone uptake by OATP2B1 has been suggested to promote progression of hormone dependent tumors. 13 alpha-estrones are effective inhibitors of endogenous estrogen formation and are potential candidates to inhibit proliferation of hormone dependent cancers. Recently, we have identified a variety of 13 alpha/beta-estrone-based inhibitors of OATP2B1. However, the nature of this interaction, whether these inhibitors are potential transported substrates of OATP2B1 and hence may be enriched in OATP2B1overexpressing cells, has not yet been investigated. In the current study we explored the antiproliferative effect of the most effective OATP2B1 inhibitor 13 alpha/beta-estrones in control and OATP2B1-overexpressing A431 carcinoma cells. We found an increased antiproliferative effect of 3-O-benzyl 13 alpha/beta-estrones in both mock transfected and OATP2B1-overexpressing cells. However, C-2 halogenated 13 alpha-estrones had a selective OATP2B1-mediated cell growth inhibitory effect. In order to demonstrate that increased sensitization can be attributed to OATP2B1-mediated cellular uptake, tritium labeled 2-bromo-13 alpha-estrone was synthesized for direct transport measurements. These experiments revealed increased accumulation of [H-3]2-bromo-13 alpha-estrone due to OATP2B1 function. Our results indicate that C-2 halogenated 13 alpha-estrones are good candidates in the design of anti-cancer drugs targeting OATP2B1. LA - English DB - MTMT ER - TY - JOUR AU - Tuerkova, Alzbeta AU - Ungvári, Orsolya AU - Laczkó-Rigó, Réka AU - Mernyák, Erzsébet AU - Szakács, Gergely AU - Laczka, Csilla AU - Zdrazil, Barbara TI - Data-Driven Ensemble Docking to Map Molecular Interactions of Steroid Analogs with Hepatic Organic Anion Transporting Polypeptides JF - JOURNAL OF CHEMICAL INFORMATION AND MODELING J2 - J CHEM INF MODEL VL - 61 PY - 2021 IS - 6 SP - 3109 EP - 3127 PG - 19 SN - 1549-9596 DO - 10.1021/acs.jcim.1c00362 UR - https://m2.mtmt.hu/api/publication/32096686 ID - 32096686 N1 - University of Vienna, Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, Althanstraße 14, Vienna, A-1090, Austria Drug Resistance Research Group, Institute of Enzymology, Rcns, Eötvös Loránd Research Network, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Medicine i, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, A-1090, Austria Export Date: 13 August 2021 CODEN: JCISD Correspondence Address: Zdrazil, B.; University of Vienna, Althanstraße 14, Austria; email: barbara.zdrazil@univie.ac.at Funding details: Austrian Science Fund, FWF, P29712 Funding details: Hungarian Scientific Research Fund, OTKA, FK 128751, SNN 124329 Funding details: National Research, Development and Innovation Office Funding text 1: B.Z. and A.T. received funding from the Austrian Science Fund (FWF), Grant P29712 (Elucidating hepatic OATP-ligand interactions and selectivity). Financial support was also received by the National Research, Development and Innovation Office. [C.Ö.-L. received funding from OTKA FK 128751; E.M. received funding from OTKA SNN 124329]. We thank Dr. Lars Richter for critical discussion especially concerning the ensemble docking procedure and Dr. Katrin Wlcek for her valuable input as a discussion partner during the grant writing phase. University of Vienna, Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, Althanstraße 14, Vienna, A-1090, Austria Drug Resistance Research Group, Institute of Enzymology, Rcns, Eötvös Loránd Research Network, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Medicine i, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, A-1090, Austria Export Date: 19 August 2021 CODEN: JCISD Correspondence Address: Zdrazil, B.; University of Vienna, Althanstraße 14, Austria; email: barbara.zdrazil@univie.ac.at Funding details: Austrian Science Fund, FWF, P29712 Funding details: Hungarian Scientific Research Fund, OTKA, FK 128751, SNN 124329 Funding details: National Research, Development and Innovation Office Funding text 1: B.Z. and A.T. received funding from the Austrian Science Fund (FWF), Grant P29712 (Elucidating hepatic OATP-ligand interactions and selectivity). Financial support was also received by the National Research, Development and Innovation Office. [C.Ö.-L. received funding from OTKA FK 128751; E.M. received funding from OTKA SNN 124329]. We thank Dr. Lars Richter for critical discussion especially concerning the ensemble docking procedure and Dr. Katrin Wlcek for her valuable input as a discussion partner during the grant writing phase. University of Vienna, Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, Althanstraße 14, Vienna, A-1090, Austria Drug Resistance Research Group, Institute of Enzymology, Rcns, Eötvös Loránd Research Network, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Medicine i, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, A-1090, Austria Export Date: 26 August 2021 CODEN: JCISD Correspondence Address: Zdrazil, B.; University of Vienna, Althanstraße 14, Austria; email: barbara.zdrazil@univie.ac.at LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Laczkó-Rigó, Réka AU - Klement, Máté AU - Kőhl, Gabriella AU - Kecskeméti, Gábor AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Design, synthesis and biological evaluation of novel estrone phosphonates as high affinity organic anion-transporting polypeptide 2B1 (OATP2B1) inhibitors JF - BIOORGANIC CHEMISTRY J2 - BIOORG CHEM VL - 112 PY - 2021 PG - 12 SN - 0045-2068 DO - 10.1016/j.bioorg.2021.104914 UR - https://m2.mtmt.hu/api/publication/32009571 ID - 32009571 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Drug Resistance Research Group instead of Membrane Protein Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Magyar tudósok körútja 2Budapest H-1117, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Export Date: 26 August 2021 LA - English DB - MTMT ER - TY - JOUR AU - Laczkó-Rigó, Réka AU - Jójárt, Rebeka AU - Mernyák, Erzsébet AU - Bakos, Éva AU - Tuerkova, Alzbeta AU - Zdrazil, Barbara AU - Laczka, Csilla TI - Structural dissection of 13-epiestrones based on the interaction with human Organic anion-transporting polypeptide, OATP2B1. JF - JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY J2 - J STEROID BIOCHEM MOL BIOL VL - 200 PY - 2020 PG - 10 SN - 0960-0760 DO - 10.1016/j.jsbmb.2020.105652 UR - https://m2.mtmt.hu/api/publication/31240434 ID - 31240434 N1 - Membrane Protein Research Group, Institute of Enzymology, RCNS, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Pharmaceutical Chemistry, Division of Drug Design and Medicinal Chemistry, University of Vienna, Althanstraße 14, Vienna, A-1090, Austria Export Date: 15 May 2020 CODEN: JSBBE Correspondence Address: Özvegy-Laczka, C.; Membrane Protein Research Group, Institute of Enzymology, RCNS, Magyar tudósok krt. 2, Hungary; email: laczka.csilla@ttk.mta.hu Chemicals/CAS: hydroxysteroid dehydrogenase, 9001-56-3 Funding details: Austrian Science Fund, FWF, P 29712 Funding details: Austrian Science Fund, FWF Funding details: Hungarian Scientific Research Fund, OTKA, SNN 124329, FK 128751 Funding text 1: This work has been supported by research grants from the National Research, Development and Innovation Office (OTKA FK 128751 and SNN 124329 ). E. M. and Cs. Ö-L. are recipients of the János Bolyai fellowship of the Hungarian Academy of Sciences. This work also received funding from the Austrian Science Fund (FWF) (Grant P 29712 ). Membrane Protein Research Group, Institute of Enzymology, RCNS, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Pharmaceutical Chemistry, Division of Drug Design and Medicinal Chemistry, University of Vienna, Althanstraße 14, Vienna, A-1090, Austria Cited By :3 Export Date: 26 August 2021 CODEN: JSBBE Correspondence Address: Özvegy-Laczka, C.; Membrane Protein Research Group, Magyar tudósok krt. 2, Hungary; email: laczka.csilla@ttk.mta.hu AB - Human OATP2B1 encoded by the SLCO2B1 gene is a multispecific transporter mediating the cellular uptake of large, organic molecules, including hormones, prostaglandins and bile acids. OATP2B1 is ubiquitously expressed in the human body, with highest expression levels in pharmacologically relevant barriers, like enterocytes, hepatocytes and endothelial cells of the blood-brain-barrier. In addition to its endogenous substrates, OATP2B1 also recognizes clinically applied drugs, such as statins, antivirals, antihistamines and chemotherapeutic agents and influences their pharmacokinetics. On the other hand, OATP2B1 is also overexpressed in various tumors. Considering that elevated hormone uptake by OATP2B1 results in increased cell proliferation of hormone dependent tumors (e.g. breast or prostate), inhibition of OATP2B1 can be a good strategy to inhibit the growth of these tumors. 13-epiestrones represent a potential novel strategy in the treatment of hormone dependent cancers by the suppression of local estrogen production due to the inhibition of the key enzyme of estrone metabolism, 17ß-hydroxysteroid-dehydrogenase type 1 (HSD17ß1). Recently, we have demonstrated that various phosphonated 13-epiestrones are dual inhibitors also suppressing OATP2B1 function. In order to gain better insights into the molecular determinants of OATP2B1 13-epiestrone interaction we investigated the effect of C-2 and C-4 halogen or phenylalkynyl modified epiestrones on OATP2B1 transport function. Potent inhibitors (with EC50 values in the low micromolar range) as well as non-inhibitors of OATP2B1 function were identified. Based on the structure-activity relationship (SAR) of the various 13-epiestrone derivatives we could define structural elements important for OATP2B1 inhibition. Our results may help to understand the drug/inhibitor interaction profile of OATP2B1, and also may be a useful strategy to block steroid hormone entry into tumors. LA - English DB - MTMT ER - TY - CONF AU - Jójárt, R AU - Pécsy, Sz AU - Szlávik, M AU - Szabó, V AU - Traj, P AU - Szécsi, Mihály AU - Laczkó-Rigó, Réka AU - Özvegy-Laczka, Cs AU - Mernyák, Erzsébet TI - Synthesis and biochemical evaluation of novel 13?-estrone derivatives for targeted intracrine modulation of estrogen biosynthesis and transport T2 - Serbian Biochemical Society - Eighth Conference PY - 2018 SP - 137 EP - 138 PG - 2 UR - https://m2.mtmt.hu/api/publication/30462098 ID - 30462098 LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Pécsy, S. AU - Keglevich, György AU - Szécsi, Mihály AU - Laczkó-Rigó, Réka AU - Laczka, Csilla AU - Kecskeméti, Gábor AU - Mernyák, Erzsébet TI - Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors JF - BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY J2 - BEILSTEIN J ORG CHEM VL - 14 ET - 0 PY - 2018 SP - 2838 EP - 2845 PG - 8 SN - 1860-5397 DO - 10.3762/bjoc.14.262 UR - https://m2.mtmt.hu/api/publication/30331520 ID - 30331520 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budapest, H-1521, Hungary 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, Szeged, H-6720, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Cited By :9 Export Date: 26 August 2021 CODEN: BJOCB Correspondence Address: Mernyák, E.; Department of Organic Chemistry, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu AB - Novel 2- or 4-phosphonated 13 alpha-estrone derivatives were synthesized via the Hirao reaction. Bromo regioisomers (2- or 4-) of 13 alpha-estrone and its 3-benzyl or 3-methyl ether were reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)(4) as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3-benzyl ether function displayed substantial submicromolar OATP2B1 inhibitory activity. The inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17 beta-hydroxysteroid dehydrogenase type 1 isozyme (17 beta-HSD1) were investigated by in vitro radiosub-strate incubation methods. None of the test compounds inhibited the STS markedly. The structure-activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17 beta-HSD1 enzyme with submicromolar IC50 values. Dual OATP2B1 and 17 beta-HSD1 inhibitors have been identified. LA - English DB - MTMT ER - TY - JOUR AU - Bacsa, Ildikó AU - Konc, C AU - Orosz, AB AU - Kecskeméti, Gábor AU - Laczkó-Rigó, Réka AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Synthesis of Novel C-2-or C-15-Labeled BODIPY-Estrone Conjugates JF - MOLECULES J2 - MOLECULES VL - 23 PY - 2018 IS - 4 PG - 13 SN - 1420-3049 DO - 10.3390/molecules23040821 UR - https://m2.mtmt.hu/api/publication/3360324 ID - 3360324 N1 - Department of Organic Chemistry, University of Szeged, Szeged, H-6720, Hungary Department of Medicinal Chemistry, University of Szeged, Dómtér 8, Szeged, H-6720, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Export Date: 30 August 2019 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of SzegedHungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; estrone, 53-16-7; 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; Alkynes; Azides; Boron Compounds; Estrone Funding details: SNN 124329 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Acknowledgments: The work of Erzsébet Mernyák and Csilla Özvegy-Laczka in this project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by National Research, Development, and Innovation Office-NKFIH through project OTKA SNN 124329. Department of Organic Chemistry, University of Szeged, Szeged, H-6720, Hungary Department of Medicinal Chemistry, University of Szeged, Dómtér 8, Szeged, H-6720, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Cited By :1 Export Date: 11 February 2020 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of SzegedHungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; estrone, 53-16-7; 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; Alkynes; Azides; Boron Compounds; Estrone Funding details: SNN 124329 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Acknowledgments: The work of Erzsébet Mernyák and Csilla Özvegy-Laczka in this project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by National Research, Development, and Innovation Office-NKFIH through project OTKA SNN 124329. Funding Agency and Grant Number: Hungarian Academy of SciencesHungarian Academy of Sciences; National Research, Development, and Innovation Office-NKFIH [OTKA SNN 124329] Funding text: The work of Erzsebet Mernyak and Csilla Ozvegy-Laczka in this project was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by National Research, Development, and Innovation Office-NKFIH through project OTKA SNN 124329. Department of Organic Chemistry, University of Szeged, Szeged, H-6720, Hungary Department of Medicinal Chemistry, University of Szeged, Dómtér 8, Szeged, H-6720, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Cited By :1 Export Date: 29 August 2020 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of SzegedHungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; estrone, 53-16-7; 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; Alkynes; Azides; Boron Compounds; Estrone Funding details: SNN 124329 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Acknowledgments: The work of Erzsébet Mernyák and Csilla Özvegy-Laczka in this project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by National Research, Development, and Innovation Office-NKFIH through project OTKA SNN 124329. Department of Organic Chemistry, University of Szeged, Szeged, H-6720, Hungary Department of Medicinal Chemistry, University of Szeged, Dómtér 8, Szeged, H-6720, Hungary Membrane protein research group, Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Cited By :1 Export Date: 10 January 2021 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of SzegedHungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; estrone, 53-16-7; 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; Alkynes; Azides; Boron Compounds; Estrone Funding details: OTKA SNN 124329 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Acknowledgments: The work of Erzsébet Mernyák and Csilla Özvegy-Laczka in this project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by National Research, Development, and Innovation Office-NKFIH through project OTKA SNN 124329. CAplus AN 2018:1757861; MEDLINE PMID: 29614041 (Journal; Article); AB - Novel BODIPY–estrone conjugates were synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Estrone-alkynes or an estrone-azide as starting compounds were synthesized via Michael addition or Sonogashira reaction as key steps. Fluorescent dyes based on BODIPY-core were provided by azide or alkyne functional groups. Fluorescent labeling of estrone was efficiently achieved at the C-2 or C-15 position. The newly-elaborated coupling procedures might have a broad applicability in the synthesis of fluorescent-labeled estrone conjugates suitable for biological assays. © 2018 by the authors. LA - English DB - MTMT ER -