TY - JOUR AU - Enyedy, Éva Anna AU - Giricz, Anett AU - Petrasheuskaya, Tatsiana AU - Mészáros, János Péter AU - May, Nóra Veronika AU - Spengler, Gabriella AU - Kovács, Ferenc AU - Molnár, Barnabás AU - Nagyné Frank, Éva TI - Comparative Solution Equilibrium Studies on Anticancer Estradiol-Based Conjugates and Their Copper Complexes JF - INORGANICS J2 - INORGANICS VL - 12 PY - 2024 IS - 2 PG - 21 SN - 2304-6740 DO - 10.3390/inorganics12020049 UR - https://m2.mtmt.hu/api/publication/34556458 ID - 34556458 AB - Steroids are often considered valuable molecular tools for the development of anticancer agents with improved pharmacological properties. Conjugation of metal chelating moieties with a lipophilic sterane backbone is a viable option to obtain novel anticancer compounds. In this work, two estradiol-based hybrid molecules (PMA-E2 and DMA-E2) with an (N,N,O) binding motif and their Cu(II) complexes were developed. The lipophilicity, solubility, and acid-base properties of the novel ligands were determined by the combined use of UV-visible spectrophotometry, pH-potentiometry, and 1H NMR spectroscopy. The solution speciation and redox activity of the Cu(II) complexes were also investigated by means of UV-visible and electron paramagnetic resonance spectroscopy. Two structurally analogous ligands (PMAP and DMAP) were also included in the studies for better interpretation of the solution chemical data obtained. Three pKa values were determined for all ligands, revealing the order of the deprotonation steps: pyridinium-NH+ or NH(CH3)2+, secondary NH2+, and OH. The dimethylamine derivatives (DMA-E2, DMAP) are found in their H2L+ forms in solution at pH 7.4, whereas the fraction of the neutral HL species is significant (34–37%) in the case of the pyridine nitrogen-containing derivatives (PMA-E2, PMAP). Both estradiol derivatives were moderately cytotoxic in human breast (MCF-7) and colon adenocarcinoma (Colo-205) cells (IC50 = 30–63 μM). They form highly stable complexes with Cu(II) ions capable of oxidizing ascorbate and glutathione. These Cu(II) complexes are somewhat more cytotoxic (IC50 = 15–45 μM) than their corresponding ligands and show a better selectivity profile. LA - English DB - MTMT ER - TY - THES AU - Molnár, Barnabás TI - Ösztránvázas aza- és oxaciklusos vegyületek régiószelektív szintézise [Regioselective synthesis of aza- and oxacyclic compounds in the estrane series] PB - Szegedi Tudományegyetem PY - 2023 SP - 86 DO - 10.14232/phd.11500 UR - https://m2.mtmt.hu/api/publication/33663106 ID - 33663106 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Molnár, Barnabás AU - Gopisetty, Mohana Krishna AU - Nagy, Ferenc István AU - Adamecz, Dóra Izabella AU - Kása, Zsolt AU - Csontné Kiricsi, Mónika AU - Nagyné Frank, Éva TI - Efficient Access to Domain-Integrated Estradiol-Flavone Hybrids Via the Corresponding Chalcones and Their in Vitro Anticancer Potential JF - STEROIDS J2 - STEROIDS VL - 187 PY - 2022 PG - 12 SN - 0039-128X DO - 10.1016/j.steroids.2022.109099 UR - https://m2.mtmt.hu/api/publication/33049036 ID - 33049036 AB - Structural modification of the phenolic A-ring of estrogens at C-2 and/or C-3 significantly reduces or eliminates the hormonal effects of the compounds, thus the incorporation of other pharmacophores into these positions can provide biologically active derivatives suitable for new indications, without possessing unwanted side effects. As part of this work, A-ring integration of estradiol with chalcones and flavones was carried out in the hope of obtaining novel molecular hybrids with anticancer action. The syntheses were performed from 2-acetylestradiol-17 beta-acetate which was first reacted with various (hetero)aromatic aldehydes in a pyrrolidine-catalyzed reaction in DMSO. The chalcones thus obtained were then subjected to oxidative cyclization with I2 in DMSO to afford estradiol-flavone hybrids in good yields. All newly synthesized derivatives were tested in vitro for cytotoxicity on human malignant cell lines of diverse origins as well as on a non-cancerous cell line, and the results demonstrated that estradiol-flavone hybrids containing a structure-integrated flavone moiety were the most active and cancer cell-selective agents. The minimal inhibitory concentration values (IC50) were calculated for selected compounds (3c, 3d and 3e) and their apoptosis inducing capacity was verified by RT-qPCR (real-time quantitative poly-merase chain reaction). The results suggest an important structure-activity relationship regarding estradiol-flavone hybrids that could form a promising synthetic platform and rationale for future drug developments. LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Barnabás AU - Njangiru, Isaac Kinyua AU - Mótyán, Gergő AU - Leits, Péter AU - Zupkó, István AU - Minorics, Renáta AU - Balogh, György Tibor AU - Nagyné Frank, Éva TI - Regioselective synthesis, physicochemical properties and anticancer activity of 2-aminomethylated estrone derivatives JF - JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY J2 - J STEROID BIOCHEM MOL BIOL VL - 219 PY - 2022 PG - 13 SN - 0960-0760 DO - 10.1016/j.jsbmb.2022.106064 UR - https://m2.mtmt.hu/api/publication/32619224 ID - 32619224 N1 - Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720, Szeged, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, H-1111, Hungary Export Date: 2 May 2022 CODEN: JSBBE Correspondence Address: Frank, É.; Department of Organic Chemistry, Hungary; email: frank@chem.u-szeged.hu Correspondence Address: Balogh, G.T.; Department of Chemical and Environmental Process Engineering, Hungary; email: balogh.gyorgy@vbk.bme.hu LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Barnabás AU - Gopisetty, Mohana Krishna AU - Adamecz, Dóra Izabella AU - Csontné Kiricsi, Mónika AU - Nagyné Frank, Éva TI - Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 PG - 20 SN - 1420-3049 DO - 10.3390/molecules25184039 UR - https://m2.mtmt.hu/api/publication/31571893 ID - 31571893 LA - English DB - MTMT ER - TY - JOUR AU - Mótyán, Gergő AU - Molnár, Barnabás AU - Wölfling, János AU - Nagyné Frank, Éva TI - Microwave-Assisted Stereoselective Heterocyclization to Novel Ring D-fused Arylpyrazolines in the Estrone Series JF - MOLECULES J2 - MOLECULES VL - 24 PY - 2019 IS - 3 PG - 15 SN - 1420-3049 DO - 10.3390/molecules24030569 UR - https://m2.mtmt.hu/api/publication/30423715 ID - 30423715 LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Anita AU - Herman, Bianka Edina AU - Görbe, Tamás AU - Mernyák, Erzsébet AU - Molnár, Barnabás AU - Wölfling, János AU - Szécsi, Mihály AU - Schneider, Gyula TI - Synthesis of novel 17-triazolyl-androst-5-en-3-ol epimers via Cu(I)-catalyzed azide-alkyne cycloaddition and their inhibitory effect on 17α-hydroxylase/C17,20-lyase JF - STEROIDS J2 - STEROIDS VL - 135 PY - 2018 SP - 79 EP - 91 PG - 13 SN - 0039-128X DO - 10.1016/j.steroids.2018.03.006 UR - https://m2.mtmt.hu/api/publication/3372993 ID - 3372993 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 Organic Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, 106 91, Sweden Cited By :2 Export Date: 29 March 2022 CODEN: STEDA Correspondence Address: Szécsi, M.; 1st Department of Medicine, Korányi fasor 8-10., Hungary Chemicals/CAS: 1,2,3 triazole derivative, 53897-99-7; azide, 12596-60-0, 14343-69-2; copper, 15158-11-9, 7440-50-8; ketoconazole, 65277-42-1; steroid 17alpha monooxygenase, 189355-97-3, 9029-67-8, 9044-50-2, 331947-43-4, 9068-00-2; lyase, 9055-04-3; Alkynes; androst-5-en-3-ol; Androstenols; Azides; Copper; Enzyme Inhibitors; Lyases; Steroid 17-alpha-Hydroxylase; Triazoles LA - English DB - MTMT ER -