TY - JOUR AU - Herman, Bianka Edina AU - Szabó, Johanna AU - Bacsa, Ildikó AU - Wölfling, János AU - Schneider, Gyula AU - Bálint, Mónika Enikő AU - Hetényi, Csaba AU - Mernyák, Erzsébet AU - Szécsi, Mihály TI - Comparative investigation of the in vitro inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1 JF - JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY J2 - J ENZYM INHIB MED CH VL - 31 PY - 2016 IS - Suppl. 3 SP - 61 EP - 69 PG - 9 SN - 1475-6366 DO - 10.1080/14756366.2016.1204610 UR - https://m2.mtmt.hu/api/publication/3097533 ID - 3097533 N1 - MTA-ELTE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, Hungary AB - The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC50 value of 1.2 μM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13β derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13β-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13β-D-secooxime has an IC50 value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature. © 2016 Informa UK Limited, trading as Taylor & Francis Group. 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 - Bacsa, Ildikó AU - Jójárt, Rebeka AU - Schneider, Gyula AU - Wölfling, János AU - Maróti, Péter AU - Herman, Bianka Edina AU - Szécsi, Mihály AU - Mernyák, Erzsébet TI - Synthesis of A-ring halogenated 13alpha-estrone derivatives as potential 17beta-HSD1 inhibitors JF - STEROIDS J2 - STEROIDS VL - 104 PY - 2015 SP - 230 EP - 236 PG - 7 SN - 0039-128X DO - 10.1016/j.steroids.2015.10.008 UR - https://m2.mtmt.hu/api/publication/2994658 ID - 2994658 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: 30 August 2019 CODEN: STEDA Correspondence Address: Szécsi, M.; 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, Hungary; email: szecsi.mihaly@med.u-szeged.hu Chemicals/CAS: testosterone 17beta dehydrogenase, 9028-62-0; estradiol 17beta dehydrogenase, 9028-61-9; estrone, 53-16-7; Enzyme Inhibitors; Estradiol Dehydrogenases; Estrone; HSD17B1 protein, human Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, K113150 Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K113150]; Richter Gedeon Plc. Funding text: The authors are grateful for financial support from the Hungarian Scientific Research Fund (OTKA K113150) and Richter Gedeon Plc. 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 :10 Export Date: 10 January 2021 CODEN: STEDA Correspondence Address: Szécsi, M.; 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, Hungary; email: szecsi.mihaly@med.u-szeged.hu Chemicals/CAS: testosterone 17beta dehydrogenase, 9028-62-0; estradiol 17beta dehydrogenase, 9028-61-9; estrone, 53-16-7; Enzyme Inhibitors; Estradiol Dehydrogenases; Estrone; HSD17B1 protein, human Funding details: Országos Tudományos Kutatási Alapprogramok, OTKA, K113150 AB - 13alpha-Estrone and its 3-methyl or benzyl ether were halogenated in ring A with N-bromo- or N-iodosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin as electrophile triggers. The chemo- and regioselectivities of the reactions depended greatly on the nature of the substituent on C-3. Bromination of the ethers led to 2- and 4-regioisomers. Bis-halogenation occurred only in the case of the phenolic derivative. Iodination and bromination resulted in similar products, except that the 3-benzyl ether could not be iodinated under the applied conditions. The potential inhibitory action of the new halogenated 13alpha-estrones on human 17beta-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Some compounds proved to be effective inhibitors, with IC50 values in the submicromolar range. LA - English DB - MTMT ER -