TY - JOUR AU - Bacsa, Ildikó AU - Jójárt, Rebeka AU - Wölfling, János AU - Schneider, Gyula AU - Herman, Bianka Edina AU - Szécsi, Mihály AU - Mernyák, Erzsébet TI - Synthesis of novel 13 alpha-estrone derivatives by Sonogashira coupling as potential 17 beta-HSD1 inhibitors JF - BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY J2 - BEILSTEIN J ORG CHEM VL - 13 PY - 2017 SP - 1303 EP - 1309 PG - 7 SN - 1860-5397 DO - 10.3762/bjoc.13.126 UR - https://m2.mtmt.hu/api/publication/3251236 ID - 3251236 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary 1st Department of Medicine, University of Szeged, Korányi fasor 8–10, Szeged, H-6720, Hungary Cited By :9 Export Date: 10 January 2021 CODEN: BJOCB Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of Szeged, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu Funding details: Hungarian Scientific Research Fund, OTKA, K113150 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: The work of Erzs?bet Merny?k in this project was supported by the J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences. This work was supported by the Hungarian Scientific Research Fund OTKA K113150. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Johanna AU - Jerkovics, N AU - Schneider, Gyula AU - Wölfling, János AU - Bózsity-Faragó, Noémi AU - Minorics, Renáta AU - Zupkó, István AU - Mernyák, Erzsébet TI - Synthesis and in Vitro Antiproliferative Evaluation of C-13 Epimers of Triazolyl-d-Secoestrone Alcohols: The First Potent 13α-D-Secoestrone Derivative JF - MOLECULES J2 - MOLECULES VL - 21 PY - 2016 IS - 5 PG - 13 SN - 1420-3049 DO - 10.3390/molecules21050611 UR - https://m2.mtmt.hu/api/publication/3067612 ID - 3067612 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 Cited By :14 Export Date: 11 February 2020 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of Szeged, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; Alcohols; Alkynes; Azides; Triazoles Funding details: K109293, K113150 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Hungarian Scientific Research Fund Funding details: Richter Gedeon Talentum Alapítvány Funding text 1: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150 and K109293). The work of No?mi B?zsity and Ren?ta Minorics was supported by a PhD Fellowship of the Talentum Fund of Richter Gedeon Plc. (Budapest) and a J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences, respectively. Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K113150, K109293]; Talentum Fund of Richter Gedeon Plc. (Budapest); Janos Bolyai Research Scholarship of the Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150 and K109293). The work of Noemi Bozsity and Renata Minorics was supported by a PhD Fellowship of the Talentum Fund of Richter Gedeon Plc. (Budapest) and a Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences, respectively. 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 Cited By :17 Export Date: 29 August 2020 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of Szeged, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; Alcohols; Alkynes; Azides; Triazoles Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Magyar Tudományos Akadémia, MTA Funding details: Hungarian Scientific Research Fund, OTKA, K109293, K113150 Funding details: Richter Gedeon Talentum AlapÃtvány Funding text 1: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150 and K109293). The work of No?mi B?zsity and Ren?ta Minorics was supported by a PhD Fellowship of the Talentum Fund of Richter Gedeon Plc. (Budapest) and a J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences, respectively. 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 Cited By :19 Export Date: 10 January 2021 CODEN: MOLEF Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of Szeged, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: azide, 12596-60-0, 14343-69-2; Alcohols; Alkynes; Azides; Triazoles Funding details: Magyar Tudományos Akadémia, MTA Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Hungarian Scientific Research Fund, OTKA, K109293, K113150 Funding details: Richter Gedeon Talentum Alapítvány Funding text 1: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150 and K109293). The work of No?mi B?zsity and Ren?ta Minorics was supported by a PhD Fellowship of the Talentum Fund of Richter Gedeon Plc. (Budapest) and a J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences, respectively. AB - The syntheses of C-13 epimeric 3-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-d-secoestrones are reported. Triazoles were prepared from 3-(prop-2-inyloxy)-d-secoalcohols and p-substituted benzyl azides via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The antiproliferative activities of the products and their precursors were determined in vitro against a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines by means of MTT assays. The orientation of the angular methyl group and the substitution pattern of the benzyl group of the azide greatly influenced the cell growth-inhibitory potential of the compounds. The 13beta derivatives generally proved to be more potent than their 13alpha counterparts. Introduction of a benzyltriazolylmethyl group onto the 3-OH position seemed to be advantageous. One 13alpha compound containing an unsubstituted benzyltriazolyl function displayed outstanding antiproliferative activities against three cell lines. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Johanna AU - Pataki, Zoltán AU - Wölfling, János AU - Schneider, Gyula AU - Bózsity-Faragó, Noémi AU - Minorics, Renáta AU - Zupkó, István AU - Mernyák, Erzsébet TI - Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents JF - STEROIDS J2 - STEROIDS VL - 113 PY - 2016 SP - 14 EP - 21 PG - 8 SN - 0039-128X DO - 10.1016/j.steroids.2016.05.010 UR - https://m2.mtmt.hu/api/publication/3078352 ID - 3078352 N1 - Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K113150, K109293]; Richter Gedeon Plc.; European UnionEuropean Union (EU); State of Hungary; European Social FundEuropean Social Fund (ESF) [TAMOP 4.2.4. A/2-11-1-2012-0001] Funding text: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150 and K109293) and Richter Gedeon Plc. This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TAMOP 4.2.4. A/2-11-1-2012-0001 'National Excellence Program'. 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 Cited By :14 Export Date: 29 August 2020 CODEN: STEDA Correspondence Address: Zupkó, I.; Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, Hungary; email: zupko@pharm.u-szeged.hu Chemicals/CAS: estrone, 53-16-7; Antineoplastic Agents; Estrone Funding details: European Social Fund, ESF Funding details: European Commission, EC Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Hungarian Scientific Research Fund, OTKA, K109293, K113150 Funding text 1: The authors are grateful for financial support from the Hungarian Scientific Research Fund ( OTKA K113150 and K109293 ) and Richter Gedeon Plc . This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP 4.2.4. A/2-11-1-2012-0001 ‘National Excellence Program’. 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 Cited By :16 Export Date: 10 January 2021 CODEN: STEDA Correspondence Address: Zupkó, I.; Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, Hungary; email: zupko@pharm.u-szeged.hu Chemicals/CAS: estrone, 53-16-7; Antineoplastic Agents; Estrone Funding details: European Social Fund, ESF Funding details: European Commission, EC Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Hungarian Scientific Research Fund, OTKA, K109293, K113150 Funding text 1: The authors are grateful for financial support from the Hungarian Scientific Research Fund ( OTKA K113150 and K109293 ) and Richter Gedeon Plc . This research was supported by the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of TÁMOP 4.2.4. A/2-11-1-2012-0001 ‘National Excellence Program’. AB - 13 alpha-Estrone derivatives containing various substituents on C-3 and C-17 were synthesized, and evaluated by means of MU assays for in vitro antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A2780 and A431). Compounds with N-benzyltriazolylmethoxy moieties on C-3 proved to be more potent than their 3-hydroxy or 3-ether counterparts. Some triazoles exerted substantial cytostatic effects against particular tumor cell lines, with submicromolar IC50 values. (C) 2016 Elsevier Inc. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Johanna AU - Bacsa, Ildikó AU - Wölfling, János AU - Schneider, Gyula AU - Zupkó, István AU - Varga, Mónika AU - Herman, Bianka Edina AU - Kalmár, László AU - Szécsi, Mihály AU - Mernyák, Erzsébet TI - Synthesis and in vitro pharmacological evaluation of N-[(1-benzyl-1,2,3-triazol-4-yl)methyl]-carboxamides on d-secoestrone scaffolds JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 31 PY - 2016 IS - 4 SP - 574 EP - 579 PG - 6 SN - 1475-6366 DO - 10.3109/14756366.2015.1050008 UR - https://m2.mtmt.hu/api/publication/2939481 ID - 2939481 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary Cereal Research Non-Profit Ltd., Szeged, Hungary 1st Department of Medicine, University of Szeged, Szeged, Hungary Department of Obstetrics and Gynecology, University of Szeged, Szeged, Hungary Cited By :14 Export Date: 23 February 2021 CODEN: JEIMA Correspondence Address: Mernyák, E.; Department of Organic Chemistry, Dóm tér 8, Hungary; email: bobe@chem.u-szeged.hu Chemicals/CAS: amide, 17655-31-1; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; estradiol 17beta dehydrogenase, 9028-61-9; estrone, 53-16-7; Antineoplastic Agents; Benzyl Compounds; D-secoestrone; Enzyme Inhibitors; Estradiol Dehydrogenases; Estrone; HSD17B1 protein, human; N-((1-benzyl-1,2,3-triazol-4-yl)methyl)carboxamide; Triazoles LA - English DB - MTMT ER - TY - JOUR AU - Mernyák, Erzsébet AU - Kovács, Ida Jusztina AU - Minorics, Renáta AU - Sere, Péter AU - Czégány, Dóra AU - Sinka, Izabella AU - Wölfling, János AU - Schneider, Gyula AU - Újfaludi, Zsuzsanna AU - Boros, Imre Miklós AU - Ocsovszki, Imre AU - Varga, Mónika AU - Zupkó, István TI - Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities JF - JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY J2 - J STEROID BIOCHEM MOL BIOL VL - 150 PY - 2015 SP - 123 EP - 134 PG - 12 SN - 0960-0760 DO - 10.1016/j.jsbmb.2015.04.001 UR - https://m2.mtmt.hu/api/publication/2878758 ID - 2878758 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 Biochemistry and Molecular Biology, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary Cereal Research Non-Profit Ltd., P.O. Box 391, Szeged, H-6701, Hungary Cited By :20 Export Date: 31 May 2021 CODEN: JSBBE Correspondence Address: Mernyák, E.; Department of Organic Chemistry, University of Szeged, Dóm tér 8, Hungary AB - Abstract Novel 16-triazoles in the 13α-estrone series were synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition of the two diastereomeric (on C-16 and on C-17) 16-azido-13α-estra-1,3,5(10)-trien-17-ol 3-benzyl ethers with substituted phenylacetylenes. The new heterocyclic derivatives were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A431, A2780, T47D, MDA-MB-231 and MDA-MB-361). The inversion of the configurations at C-16 and C-17 selectively affected the growth-inhibitory properties of the tested compounds. The 16β,17α isomers generally proved to be potent on all cell lines, with IC50 values comparable to those of the reference agent cisplatin. Change of the substitution pattern of the phenyl group of the acetylene led to great differences in antiproliferative properties. Exclusively the p-phenyl-substituted triazoles exerted high cytostatic effects. One of the most potent compounds activated caspase-3 and caspase-9 without influencing caspase-8, confirming the induction of apoptosis via the intrinsic pathway. LA - English DB - MTMT ER - TY - JOUR AU - Minorics, Renáta AU - Bózsity-Faragó, Noémi AU - Wölfling, János AU - Mernyák, Erzsébet AU - Schneider, Gyula AU - Márki, Árpád AU - Falkay, György AU - Ocsovszki, Imre AU - Zupkó, István TI - Antiproliferative effect of normal and 13-epi-d-homoestrone and their 3-methyl ethers on human reproductive cancer cell lines JF - JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY J2 - J STEROID BIOCHEM MOL BIOL VL - 132 PY - 2012 IS - 1-2 SP - 168 EP - 175 PG - 8 SN - 0960-0760 DO - 10.1016/j.jsbmb.2012.04.009 UR - https://m2.mtmt.hu/api/publication/1983613 ID - 1983613 N1 - CI: Copyright (c) 2012 Elsevier Ltd. All rights reserved. AB - The possibility of the therapeutic use of estrogens emerged following the recognition that certain estradiol analogs, and particularly metabolites (e.g. the A-ring metabolite 2-hydroxyestrone, etc.) inhibit the differentiation of diverse tumor cell lines. Until recently, despite the investigation of numerous synthetic d-ring-substituted estrone derivatives, no analysis had been published on the effects of d-ring expansion of estrone on its tumor-suppressing activity. The aim of the present study was to characterize the antiproliferative effects of normal and 13-epi-d-homoestrone and their 3-methyl ethers (1-4) on human reproductive cancer cell lines. The antitumor activities of the two epimer pairs on HeLa, MCF-7 and Ishikawa cells were determined. Normal d-homoestrone exerted the greatest cytostatic effect on HeLa cells (IC(50)=5.5muM) and was subjected to further investigations to elucidate its mechanism of action on apoptosis induction. Morphological changes detected by Hoechst 33258-propidium iodide double staining, the cell cycle arrest at phase G2/M and the subsequent increase in the proportion of the subG1 fraction determined by flow cytometric analysis and the significant increase in the activity of caspase-3 confirmed the induction of apoptosis in HeLa cells treated with d-homoestrone. d-Homoestrone was also tested on a non-cancerous human lung fibroblast cell line (MRC-5) to determine its selective toxicity. The concentration in which it inhibited cell proliferation by 50% was at least six times higher for the fibroblast cells than for cervical cancer cells. No significant in vivo estrogenic activity was observed as concerns the uterus weight of gonadectomized rats after a 7-day treatment with normal d-homoestrone. These results led to the conclusion that normal d-homoestrone is a novel antitumor compound with a similar activity on HeLa cells as that of the reference agent cisplatin, but its selectivity toward non-cancerous cells is significantly higher than that of cisplatin. It may be considered to be a basic lead molecule for the preclinical development of potential anticancer agents. LA - English DB - MTMT ER -