TY - JOUR AU - Háznagy, Márton Benedek AU - Csámpai, Antal AU - Ugrai, Imre AU - Barnabás, Molnár AU - Matti, Haukka AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Catalytical Application of Perillaldehyde-Based 3-Amino-1,2-diol Regioisomers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 25 SN - 1661-6596 DO - 10.3390/ijms25084325 UR - https://m2.mtmt.hu/api/publication/34791082 ID - 34791082 AB - A library of regioisomeric monoterpene-based aminodiols was synthesised and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The synthesis of the first type of aminodiols was achieved starting from (−)-8,9-dihydroperillaldehyde via reductive amination, followed by Boc protection and dihydroxylation with the OsO4/NMO system. Separation of formed stereoisomers resulted in a library of aminodiol diastereoisomers. The library of regioisomeric analogues was obtained starting from (−)-8,9-dihydroperillic alcohol, which was transformed into a mixture of allylic trichloroacetamides via Overman rearrangement. Changing the protecting group to a Boc function, the protected enamines were subjected to dihydroxylation with the OsO4/NMO system, leading to a 71:16:13 mixture of diastereoisomers, which were separated, affording the three isomers in isolated form. The obtained primary aminodiols were transformed into secondary derivatives. The regioselectivity of the ring closure of the N-benzyl-substituted aminodiols with formaldehyde was also investigated, resulting in 1,3-oxazines in an exclusive manner. To explain the stability difference between diastereoisomeric 1,3-oxazines, a series of comparative theoretical modelling studies was carried out. The obtained potential catalysts were applied in the reaction of aromatic aldehydes and diethylzinc with moderate to good enantioselectivities (up to 94% ee), whereas the opposite chiral selectivity was observed between secondary aminodiols and their ring-closed 1,3-oxazine analogues. LA - English DB - MTMT ER - TY - JOUR AU - Bózsity-Faragó, Noémi AU - Nagy, Viktória AU - Szabó, Johanna AU - Pálházi, Balázs AU - Kele, Zoltán AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Zupkó, István AU - Minorics, Renáta AU - Mernyák, Erzsébet TI - Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 15 SN - 1661-6596 DO - 10.3390/ijms25084274 UR - https://m2.mtmt.hu/api/publication/34789041 ID - 34789041 AB - Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges. 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 - Shakeri, Abolfazl AU - Samaei, Maryam AU - Hohmann, Judit AU - Iranshahy, Milad AU - Asili, Javad TI - C19 -diterpene alkaloids from delphinium turkmenum lipsky JF - NATURAL PRODUCT RESEARCH J2 - NAT PROD RES PY - 2024 SP - 1 EP - 5 PG - 5 SN - 1478-6419 DO - 10.1080/14786419.2024.2327618 UR - https://m2.mtmt.hu/api/publication/34777586 ID - 34777586 LA - English DB - MTMT ER - TY - JOUR AU - Bakacsy, László AU - Kardos, Luca Viktória AU - Szepesi, Ágnes AU - Nagy, Krisztina Napsugár AU - Vasas, Andrea AU - Feigl, Gábor TI - Investigation of the Allelopathic Effect of Two Invasive Plant Species in Rhizotron System JF - LIFE-BASEL J2 - LIFE-BASEL VL - 14 PY - 2024 IS - 4 PG - 15 SN - 2075-1729 DO - 10.3390/life14040475 UR - https://m2.mtmt.hu/api/publication/34771221 ID - 34771221 AB - A key question in plant invasion biology is why invasive plants are more competitive in their introduced habitat than in their native habitat. Studies show that invasive species exhibit allelopathy, influencing other plants by releasing chemicals. Research on allelopathy uses in vitro tests, investigating effects on seed germination and seedling development. Although soil plays a role in modifying allelopathic effects, observations with soil are rare and almost nothing is known about the root development of test plants developing in soil and the effects of allelopathic compounds on root architecture. Our study evaluates the allelopathic effects of false indigo-bush (Amorpha fruticosa L.) and common milkweed (Asclepias syriaca L.) on oilseed rape growth as a model plant. The rhizotron system was used to study the effect of morphology and root architecture. Leaf–soil mixtures at 0.5%, 1%, and 5% concentrations were used. Shoot and root development was strongly inhibited at 5%. But there was no difference between the allelopathy of the two species, and the application of lower concentrations did not show any effect, demonstrating that soil has a significant modifying effect on their allelopathy. Our results highlight that the development of roots growing in the soil is also worth investigating in connection with allelopathy, which can strengthen the ecological importance of allelochemicals during successful invasions. LA - English DB - MTMT ER - TY - JOUR AU - Bérczi, Bálint AU - Borbásné Farkas, Kornélia AU - Hegyi, Péter AU - Tóth, Barbara AU - Csupor, Dezső AU - Németh, Balázs AU - Lukács, Anita AU - Czumbel, László Márk AU - Kerémi, Beáta AU - Kiss, István AU - Szabó, Andrea AU - Varga, Gábor AU - Gerber, Gábor AU - Gyöngyi, Zoltán TI - Aromatase Inhibitors and Plasma Lipid Changes in Postmenopausal Women with Breast Cancer: A Systematic Review and Meta-Analysis JF - JOURNAL OF CLINICAL MEDICINE J2 - J CLIN MED VL - 13 PY - 2024 IS - 6 PG - 20 SN - 2077-0383 DO - 10.3390/jcm13061818 UR - https://m2.mtmt.hu/api/publication/34760472 ID - 34760472 N1 - Journal Article; Review AB - Background: Women are typically diagnosed with estrogen receptor-positive breast cancer around the postmenopausal period when declining estrogen levels initiate changes in lipid profiles. Aromatase inhibitors (AI) are used to prevent the progression of cancer; however, a further reduction in estrogen levels may have detrimental effects on lipid levels, which was our working hypothesis. Methods: Our meta-analysis was conducted on the lipid profiles of postmenopausal breast cancer patients at baseline and at different treatment time points. Results: We identified 15 studies, including 1708 patients. Studies using anastrozole (ANA), exemestane (EXE), letrozole (LET), and tamoxifen (TMX) were involved. Subgroup analyses revealed that 3- and 12-month administrations of LET and EXE lead to negative changes in lipid profiles that tend to alter the lipid profile undesirably, unlike ANA and TMX. Conclusions: Our results suggest that, despite statistically significant results, EXE and LET may not be sufficient to cause severe dyslipidemia in patients without cardiovascular comorbidities according to the AHA/ACC Guideline on the Management of Blood Cholesterol. However, the results may raise the question of monitoring the effects of AIs in patients, especially those with pre-existing cardiovascular risk factors such as dyslipidemia. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Barbara AU - Horváth, Attila AU - Jójártné Laczkovich, Orsolya AU - Biró, Dalma AU - Matuz, Mária AU - Csupor, Dezső TI - Storage Conditions Influence the Quality of Ginger – A Stability Study Inspired by Clinical Trials JF - PLANTA MEDICA: NATURAL PRODUCTS AND MEDICINAL PLANT RESEARCH J2 - PLANTA MED PY - 2024 SN - 0032-0943 DO - 10.1055/a-2283-8147 UR - https://m2.mtmt.hu/api/publication/34728728 ID - 34728728 N1 - Funding Agency and Grant Number: Ministry of Innovation and Technology of Hungary [TKP2021-EGA, TKP2021-EGA-32]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund Funding text: This work was supported by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme; project No. TKP2021-EGA-32 has been implemented with the support provided. AB - Ginger has traditionally been used to treat and prevent nausea and vomiting; however, the results of clinical trials are ambiguous. The efficacy of ginger is attributed to gingerols and their metabolites, shogaols. Since these compounds have different pharmacological profiles, the clinical efficacy of ginger products is largely dependent on their chemical composition. The goal of our study was to examine the stability of ginger determining the 6-gingerol contents in order to assess the effects of different storage conditions. We have performed a 6-month stability test with dry ginger rhizome samples stored in a constant climate chamber in three different storage containers (uncovered glass container, glass container sealed with rubber stopper, plastic container). 6-gingerol contents were measured by HPLC method. The concentration of 6-gingerol decreased in all samples. In the sealed glass container, the decrease of 6-gingerol content was significantly lower than in the unsealed glass container and in the plastic container. These results demonstrate that storage conditions have a significant impact on the quality of ginger, which may also affect efficacy. LA - English DB - MTMT ER - TY - JOUR AU - Vágvölgyi, Máté AU - Laczkó, Dávid AU - Santa Maria, Anaraquel AU - Vigh, Judit Piroska AU - Walter, Fruzsina AU - Berkecz, Róbert AU - Deli, Mária Anna AU - Tóth, Gábor AU - Hunyadi, Attila TI - 17-Oxime ethers of oxidized ecdysteroid derivatives modulate oxidative stress in human brain endothelial cells and dose-dependently might protect or damage the blood-brain barrier JF - PLOS ONE J2 - PLOS ONE VL - 19 PY - 2024 IS - 2 PG - 15 SN - 1932-6203 DO - 10.1371/journal.pone.0290526 UR - https://m2.mtmt.hu/api/publication/34691003 ID - 34691003 N1 - Institute of Pharmacognosy, University of Szeged, Szeged, Hungary Institute of Biophysics, HUN-REN Biological Research Centre, Szeged, Hungary Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United States Doctoral School of Biology, University of Szeged, Szeged, Hungary Institute of Pharmaceutical Analysis, University of Szeged, Szeged, Hungary NMR Group, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Budapest, Hungary Interdisciplinary Centre of Natural Products, University of Szeged, Szeged, Hungary HUN-REN-SZTE Biologically Active Natural Products Research Group, Szeged, Hungary Export Date: 18 March 2024 CODEN: POLNC Correspondence Address: Hunyadi, A.; Institute of Pharmacognosy, Hungary; email: hunyadi.attila@szte.hu AB - 20-Hydroxyecdysone and several of its oxidized derivatives exert cytoprotective effect in mammals including humans. Inspired by this bioactivity of ecdysteroids, in the current study it was our aim to prepare a set of sidechain-modified derivatives and to evaluate their potential to protect the blood-brain barrier (BBB) from oxidative stress. Six novel ecdysteroids, including an oxime and five oxime ethers, were obtained through regioselective synthesis from a sidechain-cleaved calonysterone derivative 2 and fully characterized by comprehensive NMR techniques revealing their complete 1 H and 13 C signal assignments. Surprisingly, several compounds sensitized hCMEC/D3 brain microvascular endothelial cells to tert -butyl hydroperoxide (tBHP)-induced oxidative damage as recorded by impedance measurements. Compound 8 , containing a benzyloxime ether moiety in its sidechain, was the only one that exerted a protective effect at a higher, 10 μM concentration, while at lower (10 nM– 1 μM) concentrations it promoted tBHP-induced cellular damage. Brain endothelial cells were protected from tBHP-induced barrier integrity decrease by treatment with 10 μM of compound 8 , which also mitigated the intracellular reactive oxygen species production elevated by tBHP. Based on our results, 17-oxime ethers of oxidized ecdysteroids modulate oxidative stress of the BBB in a way that may point towards unexpected toxicity. Further studies are needed to evaluate any possible risk connected to dietary ecdysteroid consumption and CNS pathologies in which BBB damage plays an important role. LA - English DB - MTMT ER - TY - JOUR AU - Shakeri, Abolfazl AU - Mirahmadi, Mohammad Reza AU - Kunert, Olaf AU - Tsai, Yu-Chi AU - Barta, Anita AU - Hohmann, Judit AU - Asili, Javad TI - Diverse diterpenoids and a triterpenoid from Euphorbia spinidens Bornm. ex Prokh JF - FITOTERAPIA J2 - FITOTERAPIA VL - 173 PY - 2024 PG - 5 SN - 0367-326X DO - 10.1016/j.fitote.2024.105838 UR - https://m2.mtmt.hu/api/publication/34556248 ID - 34556248 LA - English DB - MTMT ER - TY - JOUR AU - AHMED, Sara Hassan Hassan AU - Tayeb, Bizhar Ahmed AU - Gonda, Tímea AU - Girst, Gábor AU - Szőri, Kornél AU - Berkecz, Róbert AU - Zupkó, István AU - Minorics, Renáta AU - Hunyadi, Attila TI - Thymoquinone-protoflavone hybrid molecules as potential antitumor agents JF - PLOS ONE J2 - PLOS ONE VL - 19 PY - 2024 IS - 1 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0291567 UR - https://m2.mtmt.hu/api/publication/34541373 ID - 34541373 AB - We describe herein the synthesis of eight new ester-coupled hybrid compounds from thymoquinone and protoflavone building blocks, and their bioactivity testing against multiple cancer cell lines. Among the hybrids, compound 14 showed promising activities in all cell lines studied. The highest activities were recorded against breast cancer cell lines with higher selectivity to MDA-MB-231 as compared to MCF-7. Even though the hybrids were found to be completely hydrolysed in 24 h under cell culture conditions, compound 14 demonstrated a ca. three times stronger activity against U-87 glioblastoma cells than a 1:1 mixture of its fragments. Further, compound 14 showed good tumour selectivity: it acted 4.4-times stronger on U-87 cells than on MRC-5 fibroblasts. This selectivity was much lower, only ca. 1.3-times, when the cells were co-treated with a 1:1 mixture of its non-coupled fragments. Protoflavone-thymoquinone hybrids may therefore serve as potential new antitumor leads particularly against glioblastoma. LA - English DB - MTMT ER -