TY - JOUR AU - Khdar, Zein Alabdeen AU - Le Minh, Tam AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Szakonyi, Zsolt TI - Stereoselective synthesis and antiproliferative activity of allo-gibberic acid-based 1,3-aminoalcohols regioisomers JF - RSC MEDICINAL CHEMISTRY J2 - RSC MED CHEM VL - 15 PY - 2024 IS - 3 SP - 874 EP - 887 PG - 14 SN - 2632-8682 DO - 10.1039/D3MD00665D UR - https://m2.mtmt.hu/api/publication/34577084 ID - 34577084 AB - A new library of allo -gibberic acid-based aminoalcohol regioisomers was synthesised stereoselectively starting from commercially available gibberellic acid, which yields allo -gibberic acid under mild acidic conditions. The successful formation of hydroxymethyl... LA - English DB - MTMT ER - TY - JOUR AU - Dembo, António AU - Ferenczi, Etelka AU - Jernei, Tamás AU - Bor, Andrea AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Varga, Szilárd AU - Csámpai, Antal TI - CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine–Chalcone Hybrids JF - MOLECULES J2 - MOLECULES VL - 29 PY - 2024 IS - 2 PG - 23 SN - 1420-3049 DO - 10.3390/molecules29020375 UR - https://m2.mtmt.hu/api/publication/34499406 ID - 34499406 AB - A series of novel triazole-tethered ferrocenoylamino-substituted cinchona–chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper–enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC50 values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart. LA - English DB - MTMT ER - TY - JOUR AU - Guillon, Jean AU - Le Borgne, Marc AU - Milano, Vittoria AU - Guédin-Beaurepaire, Aurore AU - Moreau, Stéphane AU - Pinaud, Noël AU - Ronga, Luisa AU - Savrimoutou, Solène AU - Albenque-Rubio, Sandra AU - Marchivie, Mathieu AU - Kalout, Haouraa AU - Walker, Charley AU - Chevallier, Louise AU - Buré, Corinne AU - Largy, Eric AU - Gabelica, Valérie AU - Mergny, Jean-Louis AU - Baylot, Virginie AU - Ferrer, Jacky AU - Idrissi, Yamina AU - Chevret, Edith AU - Cappellen, David AU - Desplat, Vanessa AU - Schelz, Zsuzsanna AU - Zupkó, István TI - New 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazoline and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinoline Derivatives: Synthesis and Biological Evaluation as Novel Anticancer Agents by Targeting G-Quadruplex JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 17 PY - 2024 IS - 1 SN - 1424-8247 DO - 10.3390/ph17010030 UR - https://m2.mtmt.hu/api/publication/34475300 ID - 34475300 AB - The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1H,3H)-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b, 12f, and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line. LA - English DB - MTMT ER - TY - JOUR AU - Schelz, Zsuzsanna TI - Az immunszuppresszió helye a gyógyszeres terápiában JF - GYÓGYSZERÉSZET J2 - GYÓGYSZERÉSZET VL - 67 PY - 2023 IS - 5 SP - 259 EP - 262 PG - 4 SN - 0017-6036 UR - https://m2.mtmt.hu/api/publication/34432666 ID - 34432666 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Bai, Dorottya AU - Schelz, Zsuzsanna AU - Boncz, Mária Fanni AU - Zupkó, István AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpene 1,3-Aminoalcohol Regioisomers JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 24 PG - 22 SN - 1420-3049 DO - 10.3390/molecules28247962 UR - https://m2.mtmt.hu/api/publication/34417276 ID - 34417276 N1 - Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Export Date: 8 January 2024 CODEN: MOLEF Correspondence Address: Szakonyi, Z.; Interdisciplinary Excellence Center, Eötvös utca 6, Hungary; email: schelz.zsuzsanna@szte.hu Chemicals/CAS: steviol, 471-80-7; Amino Alcohols; steviol Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI, K138871, TKP2021-EGA-32 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: We are grateful for financial support from the Hungarian Research Foundation (NKFI K138871). Project no. TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. AB - A series of novel diterpene-type 1,3-aminoalcohols and their regioisomers have been synthesised from natural stevioside in a stereoselective manner. The key intermediate β-keto alcohol was prepared using Wagner–Meerwein rearrangement of the epoxide derived from steviol methyl ester. The primary aminoalcohol was formed via Raney-nickel-catalysed hydrogenation of an oxime, and a versatile library of aminoalcohols was synthesised using a Schiff base with the primary amines. The aminoalcohol regioisomers were prepared from the mesylate of the β-keto alcohols. The corresponding primary aminoalcohol was formed via the palladium-catalysed hydrogenation of hydroxyl-azide, and click reactions of the latter were also carried out. The new compounds were characterised using 1D- and 2D-NMR techniques and HRMS measurements. The in vitro investigations showed high inhibition of cell growth in human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) in the case of naphthalic N-substituted derivatives. The antiproliferative effects were assayed using the MTT method. LA - English DB - MTMT ER - TY - JOUR AU - Schelz, Zsuzsanna AU - Abdallah, Hiba Faroug Muddather AU - Zupkó, István TI - Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance JF - ANTIBIOTICS J2 - ANTIBIOTICS-BASEL VL - 12 PY - 2023 IS - 9 PG - 30 SN - 2079-6382 DO - 10.3390/antibiotics12091468 UR - https://m2.mtmt.hu/api/publication/34165889 ID - 34165889 N1 - ISSN:2079-6382 AB - Efflux pump (EP)-mediated multidrug resistance (MDR) seems ubiquitous in bacterial infections and neoplastic diseases. The diversity and lack of specificity of these efflux mechanisms raise a great obstacle in developing drugs that modulate efflux pumps. Since developing novel chemotherapeutic drugs requires large investments, drug repurposing offers a new approach that can provide alternatives as adjuvants in treating resistant microbial infections and progressive cancerous diseases. Hydroxy-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitors, also known as statins, are promising agents in this respect. Originally, statins were used in the therapy of dyslipidemia and for the prevention of cardiovascular diseases; however, extensive research has recently been performed to elucidate the functions of statins in bacterial infections and cancers. The mevalonate pathway is essential in the posttranslational modification of proteins related to vital eukaryotic cell functions. In this article, a comparative review is given about the possible role of HMG-CoA reductase inhibitors in managing diseases of bacterial and neoplastic origin. Molecular research and clinical studies have proven the justification of statins in this field. Further well-designed clinical trials are urged to clarify the significance of the contribution of statins to the lower risk of disease progression in bacterial infections and cancerous diseases. LA - English DB - MTMT ER - TY - CONF AU - Nasibova, Tohfa AU - Hohmann, Judit AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Horváth, Attila AU - Barta, Anita AU - Abdallah, Hiba Faroug Muddather ED - Hohmann, Judit TI - Chemical composition and antiproliferative properties of Peganum harmala T2 - 4th Symposium of Young Researchers on Pharmacognosy PB - Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged C1 - Szeged PY - 2023 SP - 15 EP - 15 PG - 1 DO - 10.14232/syrmpnpr.2023.9 UR - https://m2.mtmt.hu/api/publication/33941008 ID - 33941008 LA - English DB - MTMT ER - TY - CHAP AU - Abdallah, Hiba Faroug Muddather AU - Schelz, Zsuzsanna AU - Nasibova, Tohfa AU - Hohmann, Judit AU - Zupkó, István ED - Hajdú, Péter TI - In vitro Antiproliferative and Antimetastatic Proprieties of Peganum harmala T2 - XXVI. Tavaszi Szél Konferencia 2023 : Absztrakt kötet PB - Doktoranduszok Országos Szövetsége (DOSZ) CY - Budapest SN - 9786156457233 PY - 2023 SP - 345 EP - 345 PG - 1 UR - https://m2.mtmt.hu/api/publication/33939840 ID - 33939840 LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Tibor AU - Lajter, Ildikó AU - Kúsz, Norbert AU - Schelz, Zsuzsanna AU - Bózsity-Faragó, Noémi AU - Borbás, Anikó AU - Zupkó, István AU - Krupitza, Georg AU - Frisch, Richard AU - Hohmann, Judit AU - Vasas, Andrea AU - Mándi, Attila TI - Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 6 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24065841 UR - https://m2.mtmt.hu/api/publication/33708328 ID - 33708328 AB - A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells. LA - English DB - MTMT ER - TY - JOUR AU - Bai, Dorottya AU - Schelz, Zsuzsanna AU - Erdős, Dóra AU - Kis, Anna K. AU - Nagy, Viktória AU - Zupkó, István AU - Balogh, György Tibor AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Antiproliferative Activities of Tetrafunctional Diterpene Steviol Derivatives JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 2 PG - 18 SN - 1661-6596 DO - 10.3390/ijms24021121 UR - https://m2.mtmt.hu/api/publication/33547781 ID - 33547781 N1 - Interdisciplinary Excellence Center, Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös utca 6, Szeged, H-6720, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Muegyetem rkp. 3, Budapest, H-1111, Hungary Correspondence Address: Szakonyi, Z.; Interdisciplinary Excellence Center, Eötvös utca 6, Hungary; email: szakonyi.zsolt@szte.hu AB - A new family of diterpene-type aminotriol derivatives has been synthesised from stevioside in a stereoselective manner. The key intermediate spiro-epoxide was prepared through the methyl ester of the allilyc diol derived from steviol. The oxirane ring was opened with primary and secondary amines, providing a versatile library of aminotriols. The corresponding primary aminotriol was formed by palladium-catalysed hydrogenation, and an N,O-heterocyclic compound was synthesised in a regioselective reaction. All new compounds were characterised by 1D- and 2D-NMR techniques and HRMS measurements. In our in vitro investigations, we found that the aromatic N-substituted derivatives exhibited high inhibition of cell growth on human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231). The antiproliferative activities were assayed by the MTT method. Furthermore, the introduction of an additional hydroxy group slightly increased the biological activity. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements. LA - English DB - MTMT ER -