TY - JOUR AU - AHMED, Sara Hassan Hassan AU - Gonda, Tímea AU - Agbadua, Orinamhe Godwin AU - Girst, Gábor AU - Berkecz, Róbert AU - Kúsz, Norbert AU - Tsai, Meng-Chun AU - Wu, Chin-Chung AU - Balogh, György Tibor AU - Hunyadi, Attila TI - Preparation and Evaluation of 6-Gingerol Derivatives as Novel Antioxidants and Antiplatelet Agents JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 12 PY - 2023 IS - 3 PG - 18 SN - 2076-3921 DO - 10.3390/antiox12030744 UR - https://m2.mtmt.hu/api/publication/33709440 ID - 33709440 N1 - Institute of Pharmacognosy, University of Szeged, Szeged, H-6720, Hungary Institute of Pharmaceutical Analysis, University of Szeged, Szeged, H-6720, Hungary Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 807, Taiwan Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, H-6720, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Budapest, H-1111, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, H-6720, Hungary Export Date: 11 April 2023 Correspondence Address: Hunyadi, A.; Institute of Pharmacognosy, Hungary; email: hunyadi.attila@szte.hu AB - Ginger (Zingiber officinale) is widely used as a spice and a traditional medicine. Many bioactivities have been reported for its extracts and the isolated compounds, including cardiovascular protective effects. Different pathways were suggested to contribute to these effects, like the inhibition of platelet aggregation. In this study, we synthesised fourteen 6-gingerol derivatives, including eight new compounds, and studied their antiplatelet, COX-1 inhibitor, and antioxidant activities. In silico docking of selected compounds to h-COX-1 enzyme revealed favourable interactions. The investigated 6-gingerol derivatives were also characterised by in silico and experimental physicochemical and blood–brain barrier-related parameters for lead and preclinical candidate selection. 6-Shogaol (2) was identified as the best overall antiplatelet lead, along with compounds 3 and 11 and the new compound 17, which require formulation to optimize their water solubility. Compound 5 was identified as the most potent antioxidant that is also promising for use in the central nervous system (CNS). LA - English DB - MTMT ER - TY - CONF AU - Dávid, Csilla Zsuzsanna AU - Juhász, András AU - Kúsz, Norbert AU - Hohmann, Judit AU - Vasas, Andrea ED - Hohmann, Judit TI - Phytochemical investigation of a Hungarian sedge, Carex morrowii T2 - 4th Symposium of Young Researchers on Pharmacognosy PB - Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged C1 - Szeged PY - 2023 SP - 11 EP - 11 PG - 1 DO - 10.14232/syrmpnpr.2023.5 UR - https://m2.mtmt.hu/api/publication/33963414 ID - 33963414 LA - English DB - MTMT ER - TY - JOUR AU - Ferencz, Elek AU - Spengler, Gabriella AU - Zupkó, István AU - Vollár, Martin AU - Zomborszki, Zoltán Péter AU - Kúsz, Norbert AU - Hohmann, Judit AU - Kovács, Balázs AU - Csupor, Dezső AU - Laczkó-Zöld, Eszter AU - Csupor-Löffler, Boglárka TI - Isolation of compounds from the roots of Ambrosia artemisiifolia and their effects on human cancer cell lines JF - ZEITSCHRIFT FÜR NATURFORSCHUNG C-A JOURNAL OF BIOSCIENCES J2 - Z NATURFORSCH C VL - 78 PY - 2023 IS - 7-8 SP - 299 EP - 305 PG - 7 SN - 0939-5075 DO - 10.1515/znc-2022-0239 UR - https://m2.mtmt.hu/api/publication/33742452 ID - 33742452 AB - Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe with spreading use in the contemporary folk medicine. The chemical composition of the above-ground parts is extensively studied, however, the metabolites of the roots are less discovered. By multiple chromatographic purification of the root extracts, we isolated thiophene A (1), n-dodecene (2), taraxerol-3-O-acetate (3), α-linoleic acid (4), (+)-pinoresinol (5), and thiophene E (7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol) (6). The 1H NMR data published earlier for 1 were supplemented together with the assignment of 13C NMR data. Thiophene E (6), which is reported for the first time from this species, exerted cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells, whereas taraxerol-3-O-acetate (3) and α-linoleic acid (4) had slight antiproliferative effect on gynecological cancer cell lines. Thiophene E (6) and taraxerol-3-O-acetate (3) displayed antiproliferative and cytotoxic effects on MRC-5 fibroblast cells. Thiophene E (6) exerted weak antibacterial activity (MIC 25 μg/mL) on MRSA ATCC 43300, on Staphylococcus aureus ATCC 25923, Escherichia coli AG100 and E. coli ATCC 25922 both thiophenes were inactive. Although the isolated compounds exerted no remarkable cytotoxic or antiproliferative activities, the effects on MRC-5 fibroblast cells highlight the necessity of further studies to support the safety of ragweed root. LA - English DB - MTMT ER - TY - JOUR AU - Girst, Gábor AU - Lopes, Elizabeth A. AU - Goncalves, Lidia M. AU - Espadinha, Margarida AU - Kúsz, Norbert AU - Wang, Hui-Chun AU - Santos, Maria M. M. AU - Hunyadi, Attila TI - Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells JF - RSC MEDICINAL CHEMISTRY J2 - RSC MED CHEM VL - 14 PY - 2023 IS - 9 SP - 1778 EP - 1786 PG - 9 SN - 2632-8682 DO - 10.1039/d3md00251a UR - https://m2.mtmt.hu/api/publication/34261677 ID - 34261677 AB - The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments. The compounds were tested against human breast cancer cell lines MCF-7 (hormone-dependent, wild-type p53) and MDA-MB-231 (triple-negative, mutant p53). Most of the new hybrids were more cytotoxic than their reference fragments and several showed 2-4 times selective toxicity against MDA-MB-231 cells. Relevant pharmacological benefit gained from the hybrid coupling was further confirmed by virtual combination index calculations using the Chou method. Compound 13 modulated doxorubicin-induced DNA damage response through inhibiting the ATR-dependent activation of Chk-1, while increasing the activation of Chk-2. Our results suggest that the new hybrids may serve as new leads against triple negative breast cancer. 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 - Zomborszki, Zoltán Péter AU - Kúsz, Norbert AU - Hohmann, Judit AU - Csupor, Dezső TI - Three novel constituents from the roots of Rhaponticum carthamoides JF - ACTA PHARMACEUTICA HUNGARICA J2 - ACTA PHARM HUNG VL - 93 PY - 2023 IS - 1 SP - 9 EP - 14 PG - 6 SN - 0001-6659 DO - 10.33892/aph.2023.93.9-14 UR - https://m2.mtmt.hu/api/publication/33696310 ID - 33696310 LA - English DB - MTMT ER - TY - JOUR AU - Agbadua, Orinamhe Godwin AU - Kúsz, Norbert AU - Berkecz, Róbert AU - Gáti, Tamás AU - Tóth, Gábor AU - Hunyadi, Attila TI - Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 11 PY - 2022 IS - 9 PG - 14 SN - 2076-3921 DO - 10.3390/antiox11091832 UR - https://m2.mtmt.hu/api/publication/33100245 ID - 33100245 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Hungary (NKFIH) [K-134704, TKP2021-EGA-32]; (Ministry of Innovation and Technology of Hungary) Funding text: This work was supported by the National Research, Development and Innovation Office, Hungary (NKFIH; K-134704 and TKP2021-EGA-32 by the Ministry of Innovation and Technology of Hungary). AB - Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an ethoxy-substituted compound (7), and two ethoxy-substitute,0d dimers (8 and 9). Compounds 4, 7, 8, and 9 are reported here for the first time. All compounds without ethoxy substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies, compounds 2 and 4 were identified as potent competitive inhibitors of the enzyme, while compound 2 and the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound. LA - English DB - MTMT ER - TY - JOUR AU - Ahmed, SHH AU - Gonda, Tímea AU - Agbadua, Orinamhe Godwin AU - Girst, Gábor AU - Berkecz, Róbert AU - Kúsz, Norbert AU - Tsai, M-C AU - Wu, C-C AU - Balogh, György Tibor AU - Hunyadi, Attila TI - 6-Gingerol Derivatives as Promising Antiplatelet Leads JF - PLANTA MEDICA: NATURAL PRODUCTS AND MEDICINAL PLANT RESEARCH J2 - PLANTA MED VL - 88 PY - 2022 IS - 15 SP - 1514 SN - 0032-0943 DO - 10.1055/s-0042-1759193 UR - https://m2.mtmt.hu/api/publication/33686916 ID - 33686916 LA - English DB - MTMT ER - TY - JOUR AU - Dávid, Csilla Zsuzsanna AU - Kúsz, Norbert AU - Pinke, Gyula AU - Kulmány, Ágnes Erika AU - Zupkó, István AU - Hohmann, Judit AU - Vasas, Andrea TI - Jacaranone Derivatives with Antiproliferative Activity from Crepis pulchra and Relevance of This Group of Plant Metabolites JF - PLANTS-BASEL J2 - PLANTS-BASEL VL - 11 PY - 2022 IS - 6 PG - 11 SN - 2223-7747 DO - 10.3390/plants11060782 UR - https://m2.mtmt.hu/api/publication/32779416 ID - 32779416 LA - English DB - MTMT ER - TY - JOUR AU - Dávid, Csilla Zsuzsanna AU - Kúsz, Norbert AU - Stefkó, Dóra AU - Papp, L AU - Hohmann, Judit AU - Vasas, Andrea TI - Screening of the antioxidant capacity of Cyperaceae species and isolation of stilbenoids and other phenolic compounds from Carex praecox JF - PLANTA MEDICA: NATURAL PRODUCTS AND MEDICINAL PLANT RESEARCH J2 - PLANTA MED VL - 88 PY - 2022 IS - 15 SP - 1542 SN - 0032-0943 DO - 10.1055/s-0042-1759267 UR - https://m2.mtmt.hu/api/publication/33686911 ID - 33686911 LA - English DB - MTMT ER -