TY - JOUR AU - Njangiru, Isaac Kinyua AU - Bózsity-Faragó, Noémi AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Frank, Éva AU - Balogh, György Tibor AU - Zupkó, István AU - Minorics, Renáta TI - A Novel 2-Methoxyestradiol Derivative: Disrupting Mitosis-Inhibiting Cell Motility and Inducing Apoptosis in HeLa Cells In Vitro JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 5 PG - 19 SN - 1999-4923 DO - 10.3390/pharmaceutics16050622 UR - https://m2.mtmt.hu/api/publication/34840288 ID - 34840288 AB - The clinical application of 2-methoxyestradiol (2ME) in cancer therapy has been limited by its low solubility and rapid metabolism. Derivatives of 2ME have been synthesised to enhance bioavailability and decrease hepatic metabolism. Compound 4a, an analog of 2ME, has demonstrated exceptional pharmacological activity, in addition to promising pharmacokinetic profile. Our study, therefore, aimed at exploring the anticancer effects of 4a on the cervical cancer cell line, HeLa. Compound 4a exhibited a significant and dose-dependent antimetastatic and antiinvasive impact on HeLa cells, as determined by wound-healing and Boyden chamber assays, respectively. Hoechst/Propidium iodide (HOPI) double staining showcased a substantial induction of apoptosis via 4a, with minimal necrotic effect. Flow cytometry revealed a significant G2/M phase arrest, accompanied by a noteworthy rise in the sub-G1 cell population, indicating apoptosis, 18 h post-treatment. Moreover, a cell-independent tubulin polymerisation assay illustrated compound 4a’s ability to stabilise microtubules by promoting tubulin polymerisation. Molecular modelling experiments depicted that 4a interacts with the colchicine-binding site, nestled between the α and β tubulin dimers. Furthermore, 4a displayed an affinity for binding to and activating ER-α, as demonstrated by the luciferase reporter assay. These findings underscore the potential of 4a in inhibiting HPV18+ cervical cancer proliferation and cellular motility. LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Zsófia Klára AU - Koplányi, Gábor AU - Farkas, Réka AU - Péli, Noémi AU - Kenéz, Balázs AU - Decsi, Balázs AU - Katona, Gábor AU - Balogh, György Tibor AU - Vértessy, Beáta (Grolmuszné) AU - Balogh Weiser, Diána TI - Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles – A novel formulation of a therapeutic enzyme JF - INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES J2 - INT J BIOL MACROMOL VL - 268 PY - 2024 IS - Part 2 PG - 11 SN - 0141-8130 DO - 10.1016/j.ijbiomac.2024.131939 UR - https://m2.mtmt.hu/api/publication/34830192 ID - 34830192 N1 - Chemicals/CAS: calcium chloride, 10043-52-4; cysteine, 4371-52-2, 52-89-1, 52-90-4; dopachrome, 3571-34-4; ferrous chloride, 12040-57-2, 7758-94-3; ferrous sulfate, 10028-21-4, 10124-49-9, 13463-43-9, 7720-78-7, 7782-63-0, 17375-41-6, 20908-72-9; glutathione, 70-18-8; periodate sodium, 7790-28-5; potassium chloride, 7447-40-7; serine, 56-45-1, 6898-95-9; sodium chloride, 7647-14-5, 23724-87-0, 49658-21-1; tyrosine 3 monooxygenase, 9036-22-0 Tradenames: Milli-Q water purification system, Millipore, United States; Sonorex Digitec DT255 US bath, Bandelin, Germany; Thermo Scientific Multiskan SkyHigh Microplate Spectrophotometer, Thermo, United States; Thermo Scientific NanoDrop2000 spectrophotometer, Thermo, United States; Vibramax 100, Heidolph, Germany Manufacturers: Bandelin, Germany; Heidolph, Germany; Millipore, United States; Thermo, United States Funding details: European Commission, EC Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K-119493, FK-137582, K-135231 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding details: Magyar Tudományos Akadémia, MTA, TKP-6-6/PALY-2021, BO/00175/21 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, ÚNKP-23-5-BME-430, ÚNKP-22-4-II-BME-158 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding text 1: This research has been supported by the National Research Development and Innovation Office (NRDI) Fund via grant FK-137582 (D.B.W.), K-119493 (B.G.V.) and K-135231 (B.G.V.). D.B.W. also acknowledges the J\\u00E1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00175/21). The authors acknowledge the Project no. TKP-6-6/PALY-2021 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NVA funding scheme. The support of \\u00DANKP-22-4-II-BME-158 (Z.M.) and \\u00DANKP-23-5-BME-430 (D.B.W.) has been acknowledged. The research has been supported by Project RRF-2.3.1-21-2022-000 15, which has been implemented with the support provided by the European Union. AB - Human tyrosine hydroxylase (hTH) has key role in the production of catecholamine neurotransmitters. The structure, function and regulation of hTH has been extensively researched area and the possibility of enzyme replacement therapy (ERT) involving hTH through nanocarriers has been raised as well. However, our understanding on how hTH may interact with nanocarriers is still lacking. In this work, we attempted to investigate the immobilization of hTH on magnetic nanoparticles (MNPs) with various surface linkers in quantitative and mechanistic detail. Our results showed that the activity of hTH was retained after immobilization via secondary and covalent interactions as well. The colloidal stability of hTH could be also enhanced proved by Dynamic light scattering and Zeta potential analysis and a homogenous enzyme layer could be achieved, which was investigated by Raman mapping. The covalent attachment of hTH on MNPs via aldehyde or epoxy linkers provide irreversible immobilization and 38.1 % and 16.5 % recovery (ER). The hTH-MNPs catalyst had 25 % ER in average in simulated nasal electrolyte solution (SNES). This outcome highlights the relevance of immobilization applying MNPs as a potential formulation tool of sensitive therapeutic enzymes offering new opportunities for ERT related to neurodegenerative disorders. © 2024 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Gáborová, Mária AU - Vágvölgyi, Máté AU - Tayeb, Bizhar Ahmed AU - Minorics, Renáta AU - Zupkó, István AU - Jurček, Ondřej AU - Béni, Szabolcs AU - Kubínová, Renata AU - Balogh, György Tibor AU - Hunyadi, Attila TI - Diterpenes Isolated from Three Different Plectranthus Sensu Lato Species and Their Antiproliferative Activities against Gynecological and Glioblastoma Cancer Cells JF - ACS OMEGA J2 - ACS OMEGA VL - 9 PY - 2024 IS - 16 SP - 18495 EP - 18504 PG - 10 SN - 2470-1343 DO - 10.1021/acsomega.4c00800 UR - https://m2.mtmt.hu/api/publication/34779108 ID - 34779108 LA - English DB - MTMT ER - TY - JOUR AU - Csorba, Anita AU - Katona, Gábor AU - Budai-Szűcs, Mária AU - Balogh Weiser, Diána AU - Molnár, P. AU - Maka, Erika AU - Nochta-Kazsoki, Adrienn Katalin AU - Vajna, Márton Antal AU - Zelkó, Romána AU - Nagy, Zoltán Zsolt AU - Balogh, György Tibor TI - A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 3 PG - 14 SN - 1661-6596 DO - 10.3390/ijms25031623 UR - https://m2.mtmt.hu/api/publication/34538437 ID - 34538437 N1 - Department of Ophthalmology, Semmelweis University, Mária Street 39, Budapest, H-1085, Hungary Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Street 6, Szeged, H-6720, Hungary Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, H-1111, Hungary Molteam Llc., Mélyfúró Street 4, Budapest, H-1151, Hungary University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, Budapest, H-1092, Hungary Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre Street 7-9, Budapest, H-1092, Hungary Export Date: 23 February 2024 Correspondence Address: Csorba, A.; Department of Ophthalmology, Mária Street 39, Hungary; email: csorba.anita@semmelweis-univ.hu Correspondence Address: Balogh, G.T.; Department of Pharmaceutical Chemistry, Hőgyes Endre Street 7-9, Hungary; email: balogh.gyorgy.tibor@semmelweis.hu LA - English DB - MTMT ER - TY - JOUR AU - Safaa, Mohammed Omer AU - Nagy, Nándor AU - Szőcs, Emőke AU - Kádár, Szabina AU - Völgyi, Gergely AU - Pinke, Balázs AU - Mészáros, László AU - Katona, Gábor AU - Vincze, Anna AU - Dormán, Péter AU - Nagy, Zoltán Zsolt AU - Balogh, György Tibor AU - Nochta-Kazsoki, Adrienn Katalin AU - Zelkó, Romána TI - Development of innovative electrospun nepafenac-loaded nanofibers-based ophthalmic inserts JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 647 PY - 2023 PG - 13 SN - 0378-5173 DO - 10.1016/j.ijpharm.2023.123554 UR - https://m2.mtmt.hu/api/publication/34225112 ID - 34225112 N1 - University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, Budapest, H-1092, Hungary Department of Anatomy, Histology and Embryology Semmelweis University, Tűzoltó Street 58, Budapest, H-1094, Hungary Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem Rkp. 3, Budapest, H-1111, Hungary Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre Street 9, Budapest, H-1092, Hungary Department of Polymer Engineering, Faculty of Mechanical Engineering, Budapest University of Technology and Economics, Műegyetem Rkp. 3, Budapest, H-1111, Hungary Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem Rkp. 3, Budapest, H-1111, Hungary Department of Ophthalmology, Semmelweis University, Ma ́ria Street 39, Budapest, 1085, Hungary Export Date: 1 March 2024 CODEN: IJPHD Correspondence Address: Kazsoki, A.; University Pharmacy Department of Pharmacy Administration, Hőgyes Endre Street 7-9, Hungary; email: kazsoki.adrienn@semmelweis.hu Chemicals/CAS: 2 hydroxypropyl beta cyclodextrin, 94035-02-6, 128446-35-5; nepafenac, 78281-72-8; poloxamer, 9003-11-6; polyvinyl alcohol, 37380-95-3, 9002-89-5 Tradenames: nevanac Manufacturers: TCI, Japan LA - English DB - MTMT ER - TY - CONF AU - Vincze, Anna AU - Balogh, György Tibor TI - In vitro and ex vivo test systems in the development of cyclodextrin-enabled eye drops T2 - EUROCD 2023 7th European Cyclodextrin Conference PY - 2023 UR - https://m2.mtmt.hu/api/publication/34165281 ID - 34165281 LA - English DB - MTMT ER - TY - CONF AU - Erdős, Dóra AU - D. Marton, András AU - Balogh, György Tibor TI - Ginkgo biloba EGb 761® extract in vitro permeability study T2 - EUROCD 2023 7th European Cyclodextrin Conference PY - 2023 UR - https://m2.mtmt.hu/api/publication/34163444 ID - 34163444 N1 - https://www.cyclodextrinconference.com/wp-content/uploads/2023/07/EuroCD-2023-Scientific-Program-5.pdf LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Ferenc AU - Huliák, Ildikó AU - Árva, Hédi AU - Csontné Kiricsi, Mónika AU - Erdős, Dóra AU - Kocsis, Marianna AU - Takács, Gergely AU - Balogh, György Tibor AU - Nagyné Frank, Éva TI - Medicinal Chemistry‐driven Approach to Novel 2‐Substituted Benzoxazole – Estradiol Chimeras: Synthesis, Anticancer Activity and Early ADME Profile JF - CHEMMEDCHEM J2 - CHEMMEDCHEM VL - 18 PY - 2023 IS - 22 PG - 9 SN - 1860-7179 DO - 10.1002/cmdc.202300352 UR - https://m2.mtmt.hu/api/publication/34147665 ID - 34147665 N1 - Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7–8, Szeged, 6720, Hungary Department of Biochemistry and Molecular Biology, Doctoral School of Biology, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, 1111, Hungary Mcule.com Kft., Bartók Béla út 105–113, Budapest, 1115, Hungary Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. 9, Budapest, 1085, Hungary Export Date: 13 October 2023 CODEN: CHEMG Correspondence Address: Frank, É.; Department of Molecular and Analytical Chemistry, Dóm tér 7–8, Hungary; email: frank@chem.u-szeged.hu Correspondence Address: Balogh, G.T.; Department of Chemical and Environmental Process Engineering, Műegyetem rkp. 3, Hungary; email: balogh.gyorgy.tibor@semmelwies.hu AB - The efficient synthesis of novel estradiol‐based A‐ring‐fused oxazole derivatives, which can be considered as benzoxazole‐steroid domain‐integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2‐aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection‐based t‐distributed stochastic neighbor embedding (t‐SNE), the novel molecules were proved to represent a new chemical space among steroid drugs. They were characterized based on critical physicochemical parameters using in silico and experimental data. The performance of the compounds to inhibit cell proliferation was tested on four human cancer cell lines and non‐cancerous cells. Further examinations were performed to reveal IC50 and lipophilic ligand efficiency (LLE) values, cancer cell selectivity, and apoptosis‐triggering features. Pharmacological tests and LLE metric revealed that some derivatives, especially the 2‐(4‐ethylpiperazin‐1‐yl)oxazole derivative exhibit strong anticancer activity and trigger the apoptosis of cancer cells with relatively low promiscuity risk similarly to the structurally most closely‐related and intensively studied anticancer agent, 2‐methoxy‐estradiol. LA - English DB - MTMT ER - TY - JOUR AU - Juhász, Ádám AU - Ungor, Ditta Anita AU - Varga, Norbert AU - Katona, Gábor AU - Balogh, György Tibor AU - Csapó, Edit TI - Lipid-Based Nanocarriers for Delivery of Neuroprotective Kynurenic Acid: Preparation, Characterization, and BBB Transport JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 18 PG - 13 SN - 1661-6596 DO - 10.3390/ijms241814251 UR - https://m2.mtmt.hu/api/publication/34146936 ID - 34146936 AB - Encapsulation possibilities of an extensively investigated neuroprotective drug (kynurenic acid, KYNA) are studied via lipid-based nanocarriers to increase the blood–brain barrier (BBB) specific permeability. The outcomes of various preparation conditions such as stirring and sonication time, concentration of the lipid carriers and the drug, and the drug-to-lipid ratio are examined. Considering the experimentally determined encapsulation efficiency, hydrodynamic diameter, and ζ-potential values, the initial lipid and drug concentration as well as the stirring and sonication time of the preparation were optimized. The average hydrodynamic diameter of the prepared asolectin-(LIP) and water-soluble lipopolymer (WSLP)-based liposomes was found to be ca. 25 and 60 nm under physiological conditions. The physicochemical characterization of the colloidal carriers proves that the preparation of the drug-loaded liposomes was a successful process, and secondary interactions were indicated between the drug molecule and the polymer residues around the WSLP membrane. Dissolution profiles of the active molecule under physiological conditions were registered, and the release of the unformulated and encapsulated drug is very similar. In addition to this outcome, the in vitro polar brain lipid extract (porcine)-based permeability test proved the achievement of two- or fourfold higher BBB specific penetration and lipid membrane retention for KYNA in the liposomal carriers relative to the unformatted drug. LA - English DB - MTMT ER - TY - JOUR AU - Takács, Gergely AU - Havasi, Dávid AU - Sándor, Márk AU - Dohánics, Zsolt AU - Balogh, György Tibor AU - Kiss, Róbert TI - DIY Virtual Chemical Libraries - Novel Starting Points for Drug Discovery JF - ACS MEDICINAL CHEMISTRY LETTERS J2 - ACS MED CHEM LETT VL - 14 PY - 2023 IS - 9 SP - 1188 EP - 1197 PG - 10 SN - 1948-5875 DO - 10.1021/acsmedchemlett.3c00146 UR - https://m2.mtmt.hu/api/publication/34119941 ID - 34119941 LA - English DB - MTMT ER -