TY - JOUR AU - Kovács, Édua AU - Ali, Hazhmat AU - Minorics, Renáta AU - Traj, Péter AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Bruszel, Bella AU - Zupkó, István AU - Mernyák, Erzsébet TI - Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 3 PG - 17 SN - 1420-3049 DO - 10.3390/molecules28031196 UR - https://m2.mtmt.hu/api/publication/33594496 ID - 33594496 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office-NKFIH [OTKA SNN 139323, TKP2021-EGA-17] Funding text: This work was supported by National Research, Development and Innovation Office-NKFIH through projects OTKA SNN 139323 and TKP2021-EGA-17. AB - Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC50 values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin. LA - English DB - MTMT ER - TY - JOUR AU - Li, Dehong AU - Wen, Yingjie AU - Ou, Ziyue AU - Yu, Ye AU - Zhao, Chen AU - Lin, Fei AU - Xu, Hanhong TI - Inhibitor of Glucosinolate Sulfatases as a Potential Friendly Insecticide to Control Plutella xylostella JF - JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY J2 - J AGR FOOD CHEM VL - 70 PY - 2022 IS - 42 SP - 13528 EP - 13537 PG - 10 SN - 0021-8561 DO - 10.1021/acs.jafc.2c04542 UR - https://m2.mtmt.hu/api/publication/33394853 ID - 33394853 N1 - Export Date: 22 May 2023 CODEN: JAFCA Correspondence Address: Lin, F.; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangdong, China; email: resistanc@scau.edu.cn Correspondence Address: Hanhong Xu; State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangdong, China; email: hhxu@scau.edu.cn Chemicals/CAS: glycosidase, 9032-92-2; irosustat, 288628-05-7; isothiocyanic acid, 3129-90-6, 71048-69-6; sulfatase, 9068-67-1; Glucosinolates; Glycoside Hydrolases; Insecticides; irosustat; Isothiocyanates; Sulfatases AB - The glucosinolate-myrosinase system is a two-component defense system characteristic of cruciferous plants. To evade the glucosinolate-myrosinase system, the crucifer specialist insect, Plutella xylostella, promptly desulfates the glucosinolates into harmless compounds by glucosinolate sulfatases (GSSs) in the gut. In this study, we identified an effective inhibitor of GSSs by virtual screening, molecular docking analysis, and in vitro enzyme inhibition assay. The combined effect of the GSS inhibitor with the plant glucosinolate-myrosinase system was assessed by the bioassay of P. xylostella. We show that irosustat is a GSS inhibitor and the inhibition of GSSs impairs the ability of P. xylostella to detoxify the glucosinolate-myrosinase system, leading to the systematic accumulation of toxic isothiocyanates in larvae, thereby severely affecting feeding, growth, survival, and reproduction of P. xylostella. While fed on the Arabidopsis mutants deficient in myrosinase or glucosinolates, irosustat had no significant negative effect on P. xylostella. These findings reveal that the GSS inhibitor is a novel friendly insecticide to control P. xylostella utilizing the plant glucosinolate-myrosinase system and promote the development of insecticide-plant chemical defense combination strategies. LA - English DB - MTMT ER - TY - JOUR AU - Mohamed, Abdelrahman AU - Salah, Mohamed AU - Tahoun, Mariam AU - Hawner, Manuel AU - Abdelsamie, Ahmed S. AU - Frotscher, Martin TI - Dual Targeting of Steroid Sulfatase and 17 beta-Hydroxysteroid Dehydrogenase Type 1 by a Novel Drug-Prodrug Approach: A Potential Therapeutic Option for the Treatment of Endometriosis JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM PY - 2022 PG - 19 SN - 0022-2623 DO - 10.1021/acs.jmedchem.2c00589 UR - https://m2.mtmt.hu/api/publication/33394856 ID - 33394856 N1 - Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, Saarbrücken, D-66123, Germany Pharmaceutical Organic Chemistry Department, Assiut University, Assiut, 71526, Egypt Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts, Cairo, 12451, Egypt Department of Chemistry of Natural and Microbial Products, Institute of Pharmaceutical and Drug Industries Research, National Research Centre, El-Buhouth St., Dokki, P.O. Box 12622, Cairo, 12451, Egypt Department of Drug Design and Optimization, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Campus Building E81, Saarbrücken, 66123, Germany Export Date: 22 May 2023 CODEN: JMCMA Correspondence Address: Frotscher, M.; Department of Pharmacy, Campus C23, Germany; email: m.frotscher@mx.uni-saarland.de Chemicals/CAS: irosustat, 288628-05-7; steryl sulfatase, 9025-62-1; umbelliferone, 93-35-6; hydroxysteroid dehydrogenase, 9001-56-3; 17-Hydroxysteroid Dehydrogenases; 3 (or 17)-beta-hydroxysteroid dehydrogenase; Enzyme Inhibitors; Phenols; Prodrugs; Steryl-Sulfatase Tradenames: stx 64 AB - A novel approach for the dual inhibition of steroid sulfatase (STS) and 17 beta-hydroxysteroid dehydrogenase type 1(17 beta HSD1) by a single drug was explored, starting from in-house 17 beta HSD1 inhibitors via masking their phenolic OH group with a sulfamate ester. The sulfamates were intentionally designed as drugs for the inhibition of STS and, at the same time, prodrugs for 17 beta-HSD1 inhibition ("drug-prodrug approach"). The most promising sulfamates 13, 16, 18-20, 22-24, 36, and 37 showed nanomolar IC50 values for STS inhibition in a cellular assay and their corresponding phenols displayed potent 17 beta-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17 beta-HSD2, reasonable metabolic stability, and low estrogen receptor alpha affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17 beta-HSD1 inactivation. These results showed that the envisaged drug-prodrug concept was successfully implemented. The novel compounds constitute a promising class of therapeutics for the treatment of endometriosis and other estrogen-dependent diseases. LA - English DB - MTMT ER - TY - JOUR AU - Anbar, H.S. AU - Isa, Z. AU - Elounais, J.J. AU - Jameel, M.A. AU - Zib, J.H. AU - Samer, A.M. AU - Jawad, A.F. AU - El-Gamal, M.I. TI - Steroid sulfatase inhibitors: the current landscape JF - EXPERT OPINION ON THERAPEUTIC PATENTS J2 - EXPERT OPIN THER PAT VL - 31 PY - 2021 IS - 6 SP - 453 EP - 472 PG - 20 SN - 1354-3776 DO - 10.1080/13543776.2021.1910237 UR - https://m2.mtmt.hu/api/publication/32034458 ID - 32034458 N1 - Department of Clinical Pharmacy and Pharmacotherapeutics, Dubai Pharmacy College for Girls, Dubai, United Arab Emirates Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt Cited By :8 Export Date: 22 May 2023 CODEN: EOTPE Correspondence Address: Anbar, H.S.; Department of Clinical Pharmacy and Pharmacotherapeutics, United Arab Emirates; email: dr.hanan@dpc.edu Correspondence Address: El-Gamal, M.I.; College of Pharmacy, United Arab Emirates; email: drmelgamal2002@gmail.com Chemicals/CAS: irosustat, 288628-05-7; steryl sulfatase, 9025-62-1; Antineoplastic Agents; Enzyme Inhibitors; irosustat; Steryl-Sulfatase; Sulfonic Acids AB - Introduction: Steroid sulfatase (STS) enzyme is responsible for transforming the inactive sulfate metabolites of steroid sex hormones into the active free steroids. Both the deficiency and the over-expression of STS are associated with the pathophysiology of certain diseases. This article provides the readership with a comprehensive review about STS enzyme and its recently reported inhibitors. Areas covered: In the present article, we reviewed the structure, location, and substrates of STS enzyme, physiological functions of STS, and disease states related to over-expression or deficiency of STS enzyme. STS inhibitors reported during the last five years (2016-present) have been reviewed as well. Expert opinion: Irosustat is the most successful STS inhibitor drug candidate so far. It is currently under investigation in clinical trials for treatment of estrogen-dependent breast cancer. Non-steroidal sulfamate is the most favorable scaffold for STS inhibitor design. They can be beneficial for the treatment of hormone-dependent cancers and neurodegenerative disorders without significant estrogenic side effects. Moreover, dual-acting molecules (inhibitors of STS + another synergistic mechanism) can be therapeutically efficient. © 2021 Informa UK Limited, trading as Taylor & Francis Group. 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 - Jójárt, Rebeka AU - Senobar Tahaei, Seyyed Ashkan AU - Trungel-Nagy, Péter AU - Kele, Zoltán AU - Minorics, Renáta AU - Paragi, Gábor AU - Zupkó, István AU - Mernyák, Erzsébet TI - Synthesis and evaluation of anticancer activities of 2- or 4-substituted 3-(N-benzyltriazolylmethyl)-13α-oestrone derivatives JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 36 PY - 2021 IS - 1 SP - 58 EP - 67 PG - 10 SN - 1475-6366 DO - 10.1080/14756366.2020.1838500 UR - https://m2.mtmt.hu/api/publication/31645359 ID - 31645359 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 - Mernyák, Erzsébet AU - Bartha, Sándor AU - Kóczán , Lili AU - Jójárt, Rebeka AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Vágvölgyi, Máté AU - Hunyadi, Attila AU - Bruszel, Bella AU - Zupkó, István AU - Minorics, Renáta TI - Microwave-assisted Phospha-Michael addition reactions in the 13alpha-oestrone series and in vitro antiproliferative properties JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 36 PY - 2021 IS - 1 SP - 1931 EP - 1937 PG - 7 SN - 1475-6366 DO - 10.1080/14756366.2021.1963241 UR - https://m2.mtmt.hu/api/publication/32161034 ID - 32161034 LA - English DB - MTMT ER - TY - JOUR AU - Traj, Péter AU - Ali, Hazhmat AU - Motzwickler-Németh, Anett AU - Dajcs, Sámuel Trisztán AU - Tömösi, Ferenc AU - Tea, Lanisnik-Rizner AU - Zupkó, István AU - Mernyák, Erzsébet TI - Transition metal-catalyzed A-ring C–H activations and C(sp2)–C(sp2) couplings in the 13α-estrone series and in vitro evaluation of antiproliferative properties JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 36 PY - 2021 IS - 1 SP - 895 EP - 902 PG - 8 SN - 1475-6366 DO - 10.1080/14756366.2021.1900165 UR - https://m2.mtmt.hu/api/publication/31916683 ID - 31916683 LA - English DB - MTMT ER - TY - JOUR AU - Sinreih, Maša AU - Jójárt, Rebeka AU - Kele, Zoltán AU - Büdefeld, Tomaž AU - Paragi, Gábor AU - Mernyák, Erzsébet AU - Rižner, Tea Lanišnik TI - Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 36 PY - 2021 IS - 1 SP - 1500 EP - 1508 PG - 9 SN - 1475-6366 DO - 10.1080/14756366.2021.1937142 UR - https://m2.mtmt.hu/api/publication/32096593 ID - 32096593 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 - Adhikari, Nilanjan AU - Baidya, Sandip Kumar AU - Jha, Tarun TI - Effective anti-aromatase therapy to battle against estrogen-mediated breast cancer: Comparative SAR/QSAR assessment on steroidal aromatase inhibitors JF - EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY J2 - EUR J MED CHEM VL - 208 PY - 2020 SN - 0223-5234 DO - 10.1016/j.ejmech.2020.112845 UR - https://m2.mtmt.hu/api/publication/31848935 ID - 31848935 N1 - Cited By :1 Export Date: 29 July 2021 CODEN: EJMCA Correspondence Address: Jha, T.; Natural Science Laboratory, P. O. Box 17020, India; email: tjupharm@yahoo.com Chemicals/CAS: aromatase, 9039-48-9; formestane, 566-48-3; Antineoplastic Agents; Aromatase; Aromatase Inhibitors; Estrogens LA - English DB - MTMT ER - TY - JOUR AU - Canario, Catarina AU - Matias, Mariana AU - de Brito, Vanessa AU - Santos, Adriana O. AU - Falcao, Amilcar AU - Silvestre, Samuel AU - Alves, Gilberto TI - Delta(9,11)-Estrone derivatives as potential antiproliferative agents: synthesis, in vitro biological evaluation and docking studies JF - COMPTES RENDUS CHIMIE J2 - CR CHIM VL - 23 PY - 2020 IS - 2 SP - 201 EP - 217 PG - 17 SN - 1631-0748 DO - 10.5802/crchim.17 UR - https://m2.mtmt.hu/api/publication/31689996 ID - 31689996 N1 - CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal CIBIT - Coimbra, Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal Cited By :3 Export Date: 8 May 2023 CODEN: CRCOC Correspondence Address: Silvestre, S.; CICS-UBI - Health Sciences Research Centre, Portugal; email: samuel@fcsaude.ubi.pt AB - A series of Delta(9,11)-estrone derivatives with A- and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, llepaRG, Caco-2 and NUM.) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly Delta(9,11)-estrone, which was the most active against llepaRG cells (IC50 = 6.67 mu M). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for I lepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with Delta(9,11)-estrone and a cell cycle arrest at the G(0)/G(1) phase. Estrogenic activity was also observed for this compound at 0.1 mu M in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor alpha. LA - English DB - MTMT ER - TY - JOUR AU - Dasko, Mateusz AU - Demkowicz, Sebastian AU - Biernacki, Karol AU - Ciupak, Olga AU - Kozak, Witold AU - Maslyk, Maciej AU - Rachon, Janusz TI - Recent progress in the development of steroid sulphatase inhibitors - examples of the novel and most promising compounds from the last decade JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 35 PY - 2020 IS - 1 SP - 1163 EP - 1184 PG - 22 SN - 1475-6366 DO - 10.1080/14756366.2020.1758692 UR - https://m2.mtmt.hu/api/publication/31501725 ID - 31501725 N1 - Department of Inorganic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland Department of Physical Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland Department of Molecular Biology, Faculty of Biotechnology and Environment Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland Cited By :1 Export Date: 23 February 2021 CODEN: JEIMA Correspondence Address: Daśko, M.; Department of Inorganic Chemistry, Narutowicza 11/12, Poland; email: mateusz.dasko@pg.edu.pl Chemicals/CAS: estradiol, 50-28-2; irosustat, 288628-05-7; steryl sulfatase, 9025-62-1; Enzyme Inhibitors; Steryl-Sulfatase; STS protein, human AB - The purpose of this review article is to provide an overview of recent achievements in the synthesis of novel steroid sulphatase (STS) inhibitors. STS is a crucial enzyme in the biosynthesis of active hormones (including oestrogens and androgens) and, therefore, represents an extremely attractive molecular target for the development of hormone-dependent cancer therapies. The inhibition of STS may effectively reduce the availability of active hormones for cancer cells, causing a positive therapeutic effect. Herein, we report examples of novel STS inhibitors based on steroidal and nonsteroidal cores that contain various functional groups (e.g. sulphamate and phosphorus moieties) and halogen atoms, which may potentially be used in therapies for hormone-dependent cancers. The presented work also includes examples of multitargeting agents with STS inhibitory activities. Furthermore, the fundamental discoveries in the development of the most promising drug candidates exhibiting STS inhibitory activities are highlighted. LA - English DB - MTMT ER - TY - JOUR AU - Herman, Bianka Edina AU - Gardi, János AU - Julesz, János AU - Tömböly, Csaba AU - Szánti-Pintér, Eszter AU - Fehér, Klaudia AU - Skodáné Földes, Rita AU - Szécsi, Mihály TI - Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 71 PY - 2020 IS - 3 SP - 249 EP - 264 PG - 16 SN - 2676-8615 DO - 10.1007/s42977-020-00023-7 UR - https://m2.mtmt.hu/api/publication/31365295 ID - 31365295 LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Ali, Hazhmat AU - Horváth, Gergely AU - Kele, Zoltán AU - Zupkó, István AU - Mernyák, Erzsébet TI - Pd-Catalyzed Suzuki–Miyaura couplings and evaluation of 13α-estrone derivatives as potential anticancer agents JF - STEROIDS J2 - STEROIDS VL - 164 PY - 2020 PG - 10 SN - 0039-128X DO - 10.1016/j.steroids.2020.108731 UR - https://m2.mtmt.hu/api/publication/31606817 ID - 31606817 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6., Szeged, H-6720, Hungary Department of Medicinal Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Export Date: 10 January 2021 CODEN: STEDA Correspondence Address: Zupkó, I.; Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6., Hungary Chemicals/CAS: cisplatin, 15663-27-1, 26035-31-4, 96081-74-2 Manufacturers: Ebewe, Austria Funding details: Emberi Eroforrások Minisztériuma, EMMI Funding details: Magyar Tudományos Akadémia, MTA, ÚNKP-19-4-SZTE-71 Funding details: 20391-3/2018/FEKUSTRAT, OTKA SNN 124329 Funding text 1: The work of Erzsébet Mernyák in this project was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The work of Erzsébet Mernyák in this project was supported by the ÚNKP-19-4-SZTE-71, New National Excellence Program of The Ministry of Human CapacitieS”. This work was supported by National Research, Development and Innovation Office-NKFIH through project OTKA SNN 124329. Support from Ministry of Human Capacities, Hungary grant 20391-3/2018/FEKUSTRAT is acknowledged. LA - English DB - MTMT ER - TY - JOUR AU - Kharb, Rajeev AU - Haider, Kashif AU - Neha, Kumari AU - Yar, Mohammad S. TI - Aromatase inhibitors: Role in postmenopausal breast cancer JF - ARCHIV DER PHARMAZIE J2 - ARCH PHARM VL - 353 PY - 2020 IS - 8 PG - 20 SN - 0365-6233 DO - 10.1002/ardp.202000081 UR - https://m2.mtmt.hu/api/publication/31453011 ID - 31453011 N1 - Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard (Deemed-to-be-University), New Delhi, India Cited By :29 Export Date: 22 May 2023 CODEN: ARPMA Correspondence Address: Yar, M.S.; Department of Pharmaceutical Chemistry, India; email: yarmsy@rediffmail.com Chemicals/CAS: aminoglutethimide, 125-84-8; anastrozole, 120511-73-1; exemestane, 107868-30-4; fadrozole, 102676-31-3; formestane, 566-48-3; letrozole, 112809-51-5; testolactone, 968-93-4; vorozole, 118949-22-7, 129731-10-8; aromatase, 9039-48-9; Antineoplastic Agents; Aromatase; Aromatase Inhibitors Tradenames: afema; arimidex; aromasin; bio letrazole; cytadren; elipten; femara; fludestrin; lentaron; rivizor; teslac AB - Postmenopausal women are at high risk of developing breast cancer due to estrogen production in peripheral tissues of the body other than ovaries. Aromatase is present in breast tissue, leading to local estrogen production which can be inhibited by a variety of steroidal and nonsteroidal aromatase inhibitors. There are many aromatase inhibitors available in clinical practice like exemestane, formestane, anastrozole, letrozole, fadrozole, vorozole, and so forth, but the major challenge in anti-breast cancer therapy is the toxicity associated with aromatase inhibitors, especially the steroidal class of drugs. It is, therefore, urgently required to develop novel anticancer drugs having better safety and efficacy for the treatment of breast cancer. This study highlights the aromatase inhibitors reported in the current literature as well as the recent advances in the management of breast cancer. 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 - JOUR AU - Patel, Pritesh R. AU - Henderson, Scott H. AU - Roe, Mark S. AU - Honey, Mark A. TI - Decarboxylative Bromination of Heteroarenes: Initial Mechanistic Insights JF - SYNLETT J2 - SYNLETT VL - 31 PY - 2020 IS - 16 SP - 1603 EP - 1607 PG - 5 SN - 0936-5214 DO - 10.1055/s-0040-1707901 UR - https://m2.mtmt.hu/api/publication/31692545 ID - 31692545 N1 - Export Date: 23 February 2021 CODEN: SYNLE Correspondence Address: Honey, M.A.; School of Science, United Kingdom; email: m.a.honey@gre.ac.uk AB - After an initial report from our laboratory describing metal-free decarboxylative halogenation of various azaheteroarenes, we set out to investigate the possible mechanism by which this chemistry occurs. Evidence from this mechanistic investigation suggests that this chemistry occurs via a radical pathway, with(1)H NMR studies suggesting that the acidic substrates activate NBS. LA - English DB - MTMT ER - TY - JOUR AU - Guo, Wei-Yun AU - Zeng, Shang-Ming-Zhu AU - Deora, Girdhar Singh AU - Li, Qing-Shan AU - Ruan, Ban-Feng TI - Estrogen Receptor alpha (ER alpha)-targeting Compounds and Derivatives: Recent Advances in Structural Modification and Bioactivity JF - CURRENT TOPICS IN MEDICINAL CHEMISTRY J2 - CURR TOP MED CHEM VL - 19 PY - 2019 IS - 15 SP - 1318 EP - 1337 PG - 20 SN - 1568-0266 DO - 10.2174/1568026619666190619142504 UR - https://m2.mtmt.hu/api/publication/31575515 ID - 31575515 N1 - School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China Monash Institute of Pharmaceutical Sciences, Monash University, ParkvilleVIC 3052, Australia Cited By :3 Export Date: 23 February 2021 CODEN: CTMCC Correspondence Address: Deora, G.S.; School of Food and Biological Engineering, China; email: girdhar.deora@monash.edu Chemicals/CAS: Antineoplastic Agents; Aromatase Inhibitors; Estrogen Receptor alpha; Estrogen Receptor Antagonists; Estrogen Receptor Modulators AB - Breast cancer is the most common cancer suffered by female, and the second highest cause of cancer-related death among women worldwide. At present, hormone therapy is still the main treatment route and can be divided into three main categories: selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). However, breast cancer is difficult to cure even after several rounds of anti-estrogen therapy and most drugs have serious side-effects. Here, we review the literature published over the past five years regarding the isolation and synthesis of analogs and their derivatives. LA - English DB - MTMT ER - TY - JOUR AU - Jójárt, Rebeka AU - Traj, Péter AU - Kovács, Édua AU - Horváth, Ágnes AU - Schneider, Gyula AU - Szécsi, Mihály AU - Pál, Attila AU - Paragi, Gábor AU - Mernyák, Erzsébet TI - Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors JF - MOLECULES J2 - MOLECULES VL - 24 PY - 2019 IS - 9 PG - 18 SN - 1420-3049 DO - 10.3390/molecules24091783 UR - https://m2.mtmt.hu/api/publication/30672179 ID - 30672179 N1 - WoS:hiba:000469518100142 2020-01-10 07:35 cikkazonosító nem egyezik LA - English DB - MTMT ER - TY - JOUR AU - Lauro, Figueroa-Valverde AU - Abelardo, Camacho-Luis AU - Francisco, Diaz-Cedillo AU - Marcela, Rosas-Nexticapa AU - Virginia, Mateu-Armand AU - Patricia, Hernandez-Vasquez AU - Eduardo, Pool-Gomez AU - Maria, Lopez-Ramos AU - Lenin, Hau-Heredia AU - Tomas Joel, Lopez-Gutierrez AU - Bety, Sarabia-Alcocer AU - Alondra, Alfonso-Jimenez AU - Jhair, Cabrera-Tuz TI - Preparation of two steroid derivatives and its theoretical interaction with a 17 beta-hydroxysteroid dehydrogenase type 1 JF - BIOINTERFACE RESEARCH IN APPLIED CHEMISTRY J2 - BIOINTERF RES APPL CHEM VL - 9 PY - 2019 IS - 1 SP - 3800 EP - 3805 PG - 6 SN - 2069-5837 DO - 10.33263/BRIAC91.800805 UR - https://m2.mtmt.hu/api/publication/30555885 ID - 30555885 AB - The aim of this study was synthesizing two steroid derivatives to evaluate their theoretical interact with a 17 beta-hydroxysteroid dehydrogenase type 1. The first stage was achieved by the preparation of a steroid-imino analog (compound 2) using a reaction of imination and ii) etherification. Then, the theoretical interact of two steroid analogs with 17 beta-hydroxysteroid dehydrogenase type 1 (IIOL) was evaluated using fisetin and methyl paraben as controls in a docking model. The results suggest that steroid derivatives could interact via a different type of aminoacid residues of IIOL protein surface. However, the compound 2 showed a constant of inhibition lower compared with fisetin, methyl paraben and compound 3. All these data indicate that steroid derivative could act as 17 beta-hydroxysteroid dehydrogenase type 1 inhibitor. 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 -