116 results on '"Attila Mándi"'
Search Results
2. VCD Analysis of Axial Chirality in Synthetic Stereoisomeric Biaryl-Type bis-Isochroman Heterodimers with Isolated Blocks of Central and Axial Chirality
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Zoltán Czenke, Attila Mándi, Sándor Balázs Király, Attila Kiss-Szikszai, Anita Kónya-Ábrahám, Anna Kurucz-Szabados, Krisztián Cserepes, Attila Bényei, Changsheng Zhang, Máté Kicsák, and Tibor Kurtán
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stereogenic biaryl axis ,stereoisomeric bis-isochromans ,isolated blocks of chirality ,VCD ,ECD ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Optically active heterodimeric 5,5′-linked bis-isochromans, containing a stereogenic ortho-trisubstituted biaryl axis and up to four chirality centers, were synthesized stereoselectively by using a Suzuki–Miyaura biaryl coupling reaction of optically active isochroman and 1-arylpropan-2-ol derivatives, providing the first access to synthetic biaryl-type isochroman dimers. Enantiomeric pairs and stereoisomers up to seven derivatives were prepared with four different substitution patterns, which enabled us to test how OR, ECD, and VCD measurements and DFT calculations can be used to determine parallel central and axial chirality elements in three isolated blocks of chirality. In contrast to natural penicisteckins A–D and related biaryls, the ECD spectra and OR data of (aS) and (aR) atropodiastereomers did not reflect the opposite axial chirality, but they were characteristic of the central chirality. The atropodiastereomers showed consistently near-mirror-image VCD curves, allowing the determination of axial chirality with the aid of DFT calculation or by comparison of characteristic VCD transitions.
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- 2024
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3. Testing the Simplified Molecular Dynamics Approach to Improve the Reproduction of ECD Spectra and Monitor Aggregation
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Attila Mándi, Aliz Rimóczi, Andrea Vasas, Judit Hohmann, Mahadeva M. M. Swamy, Kenji Monde, Roland A. Barta, Máté Kicsák, István Komáromi, Krisztina Fehér, and Tibor Kurtán
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electronic circular dichroism ,molecular mechanics ,enhancement of agreement ,aggregation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
A simplified molecular-dynamics-based electronic circular dichroism (ECD) approach was tested on three condensed derivatives with limited conformational flexibility and an isochroman-2H-chromene hybrid, the ECD spectra of which could not be precisely reproduced by the conventional ECD calculation protocol. Application of explicit solvent molecules at the molecular mechanics (MD) level in the dynamics simulations and subsequent TDDFT-ECD calculation for the unoptimized MD structures was able to improve the agreements between experimental and computed spectra. Since enhancements were achieved even for molecules with limited conformational flexibility, deformations caused by the solvent molecules and multitudes of conformers produced with unoptimized geometries seem to be key factors for better agreement. The MD approach could confirm that aggregation of the phenanthrene natural product luzulin A had a significant contribution to a specific wavelength range of the experimental ECD. The MD approach has proved that dimer formation occurred in solution and this was responsible for the anomalous ECD spectrum. The scope and limitations of the method have also been discussed.
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- 2024
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4. Flavin-enabled reductive and oxidative epoxide ring opening reactions
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Bidhan Chandra De, Wenjun Zhang, Chunfang Yang, Attila Mándi, Chunshuai Huang, Liping Zhang, Wei Liu, Mark W. Ruszczycky, Yiguang Zhu, Ming Ma, Ghader Bashiri, Tibor Kurtán, Hung-wen Liu, and Changsheng Zhang
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Science - Abstract
Epoxide ring opening reactions are important in both biological processes and synthetic applications. Here, the authors show that flavin cofactors can catalyze reductive and oxidative epoxide ring opening reactions and propose the underlying mechanisms.
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- 2022
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5. New Meroterpenoid Derivatives from the Pomegranate-Derived Endophytic Fungus Talaromyces purpureogenus
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Alaa Anwar, Mohamed S. Elnaggar, Ahmed M. Elissawy, Nehal Ibrahim, Attila Mándi, Tibor Kurtán, Zhen Liu, Sherweit H. El-Ahmady, and Rainer Kalscheuer
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Talaromyces purpureogenus ,endophytes ,meroterpenoids ,structural elucidation ,absolute configuration ,antimicrobial activity ,Organic chemistry ,QD241-441 - Abstract
In this study, we report the isolation of two new meroterpenoids, miniolutelide D (1) and miniolutelide E (13-epi-miniolutelide C) (2), along with two meroterpenoidal analogues (3 and 4) and two phenolic compounds (5 and 6) from the endophytic fungus Talaromyces purpureogenus derived from Punica granatum fruits. Their structures were elucidated using extensive MS, 1D, and 2D NMR spectroscopic analyses as well as by comparing with data in the literature. The absolute configurations of 1 and 2 were determined using TDDFT-ECD calculations. Antimicrobial activity was evaluated. Compound 5 displayed significant activity against methicillin-resistant Staphylococcus aureus strain ATCC 700699 and moderate activity against S. aureus strain ATCC 29213.
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- 2023
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6. Panapophenanthrin, a Rare Oligocyclic Diterpene from Panus strigellus
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Natalia A. Llanos-López, Sherif Saeed Ebada, Aída M. Vasco-Palacios, Laura M. Sánchez-Giraldo, Lina López, Luisa F. Rojas, Attila Mándi, Tibor Kurtán, and Yasmina Marin-Felix
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basidiomycota ,antimicrobial ,cytotoxicity ,secondary metabolites ,white rot fungi ,Microbiology ,QR1-502 - Abstract
During the course of our search for biologically active secondary metabolites from fungal cultures, a new oligocyclic diterpenoidal derivative, panapophenanthrin (1), was isolated from Panus strigellus. In addition, two known metabolites, panepophenanthrin (2) and dihydrohypnophilin (3), were also obtained. The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectral analyses together with high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configuration was determined through TDDFT-ECD calculations. All of the compounds were assessed for their antimicrobial and cytotoxic activities. Compounds 1 and 3 showed moderate to weak activities in the performed antimicrobial assays, while compound 1 exhibited potent cytotoxic activity against the mammalian cell lines mouse fibroblast (L929) and human endocervical adenocarcinoma (KB3.1).
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- 2023
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7. Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata
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Tibor Kovács, Ildikó Lajter, Norbert Kúsz, Zsuzsanna Schelz, Noémi Bózsity-Faragó, Anikó Borbás, István Zupkó, Georg Krupitza, Richard Frisch, Judit Hohmann, Andrea Vasas, and Attila Mándi
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natural product ,stereochemistry ,NMR shift parameter development ,DFT calculations ,ECD calculations ,antiproliferative activity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
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.
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- 2023
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8. In Vitro Biological Activity of Natural Products from the Endophytic Fungus Paraboeremia selaginellae against Toxoplasma gondii
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Flaminia Mazzone, Viktor E. Simons, Lasse van Geelen, Marian Frank, Attila Mándi, Tibor Kurtán, Klaus Pfeffer, and Rainer Kalscheuer
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Toxoplasma gondii ,Paraboeremia selaginellae ,endophytic fungi ,natural products ,bioactivity ,biphenyl ether ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Toxoplasma gondii is an apicomplexan pathogen able to infect a wide range of warm-blooded animals, including humans, leading to toxoplasmosis. Current treatments for toxoplasmosis are associated with severe side-effects and a lack efficacy to eradicate chronic infection. Thus, there is an urgent need for developing novel, highly efficient agents against toxoplasmosis with low toxicity. For decades, natural products have been a useful source of novel bioactive compounds for the treatment of infectious pathogens. In the present study, we isolated eight natural products from the crude extract of the endophytic fungus Paraboeremia selaginellae obtained from the leaves of the plant Philodendron monstera. The natural products were tested for inhibiting Toxoplasma gondii proliferation, and their cytotoxicity was evaluated in different human cell lines. Six natural products showed antitoxoplasma activity with low or no cytotoxicity in human cell lines. Together, these findings indicate that biphenyl ethers, bioxanthracenes, and 5S,6S-phomalactone from P. selaginellae are potential candidates for novel anti-toxoplasma drugs.
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- 2022
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9. Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
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Ying Gao, Fabian Stuhldreier, Laura Schmitt, Sebastian Wesselborg, Zhiyong Guo, Kun Zou, Attila Mándi, Tibor Kurtán, Zhen Liu, and Peter Proksch
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Aplosporella javeedii ,lactam derivatives ,OSMAC approach ,DFT-NMR ,TDDFT-ECD ,OR calculations ,Microbiology ,QR1-502 - Abstract
Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO3 or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC50 values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.
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- 2020
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10. Synthesis and Vibrational Circular Dichroism Analysis of N-Heterocyclic Carbene Precursors Containing Remote Chirality Centers
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Zita Szabó, Attila Paczal, Tibor Kovács, Attila Mándi, Andras Kotschy, and Tibor Kurtán
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DFT calculations ,characteristic VCD transitions ,electronic circular dichroism ,conformational analysis ,NHC precursors ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
VCD analysis of 16 diastereomeric pairs of NHC precursors containing two isolated chirality centers and different substitution patterns identified VCD transitions characteristic of the chirality center in the imidazolium ring or in the side chain, which, in contrast to ECD and OR, could be utilized to assign the two chirality centers separately by simple comparison, regardless of the type and position of achiral aromatic substituents. While the ECD and OR data showed great dependence on the position of an achiral substituent such as a methoxy group, characteristic experimental VCD transitions remained consistent and they could be used to determine the absolute configuration of all the regio- and stereoisomers and substituted analogues. VCD, ECD and OR approaches were evaluated, and several carbene precursors were found, for which only the VCD method could distinguish the four stereoisomers. With t-butyl, phenyl or 2-naphthyl substituents at the C-1′ chirality center, the ECD spectra of the C-1′ epimers were near-identical, and hence it was only the VCD approach that showed distinct differences suitable for the configurational assignment. The chiroptical characterization of our diastereomeric pairs of NHC precursors enables the future application of related derivatives having different substitution patterns in stereoselective transformations.
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- 2022
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11. Zizaane-Type Sesquiterpenoids and Their Rearranged Derivatives from Agarwood of an Aquilaria Plant
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Jing-Zhe Yuan, Yi-Ling Yang, Wei Li, Li Yang, Hao-Fu Dai, Attila Mándi, Cai-Hong Cai, Hui-Qin Chen, Wen-Hua Dong, Tibor Kurtán, Wen-Li Mei, and Hao Wang
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agarwood ,Aquilaria sp. ,sesquiterpenoid ,zizaane ,TDDFT-ECD ,anti-inflammatory effect ,Organic chemistry ,QD241-441 - Abstract
Nine new sesquiterpenoids (1–9) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp., including three novel sesquiterpenoids (1–3) derived from zizaane, together with six zizaane-type sesquiterpenoids (4–9). All structures were unambiguously elucidated based on 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of sesquiterpenoids was determined by comparison of the experimental and computed ECD spectra. In vitro anti-inflammatory assessment showed that compound 9 exhibited inhibition of NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 62.22 ± 1.27 μM.
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- 2021
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12. Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells
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Andrea Vasas, Ildikó Lajter, Norbert Kúsz, Sándor Balázs Király, Tibor Kovács, Tibor Kurtán, Noémi Bózsity, Nikolett Nagy, Zsuzsanna Schelz, István Zupkó, Georg Krupitza, Richard Frisch, Attila Mándi, and Judit Hohmann
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Neurolaena lobata ,Asteraceae ,germacranolides ,eudesmanes ,isodaucane ,sesquiterpenes ,Pharmacy and materia medica ,RS1-441 - Abstract
Seven new germacranolides (1–3, 5–8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata. Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, 13C and 1H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds (1–10) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C (6) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells.
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- 2021
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13. Neuronal Modulators from the Coral-Associated Fungi Aspergillus candidus
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Gao-Yang Peng, Tibor Kurtán, Attila Mándi, Jing He, Zheng-Yu Cao, Hua Tang, Shui-Chun Mao, and Wen Zhang
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coral-associated fungi ,secondary metabolites ,p-terphenyl ,indole-diterpene alkaloids ,spontaneous Ca2+ oscillations ,Biology (General) ,QH301-705.5 - Abstract
Three new p-terphenyl derivatives, named 4″-O-methyl-prenylterphenyllin B (1) and phenylcandilide A and B (17 and 18), and three new indole-diterpene alkaloids, asperindoles E–G (22-24), were isolated together with eighteen known analogues from the fungi Aspergillus candidus associated with the South China Sea gorgonian Junceela fragillis. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic analysis, and DFT/NMR and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, the compounds 6, 9, 14, 17, 18 and 24 modulated spontaneous Ca2+ oscillations and 4-aminopyridine hyperexcited neuronal activity. A preliminary structure–activity relationship was discussed.
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- 2021
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14. Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B
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Viktor Ilkei, András Spaits, Anita Prechl, Áron Szigetvári, Zoltán Béni, Miklós Dékány, Csaba Szántay Jr, Judit Müller, Árpád Könczöl, Ádám Szappanos, Attila Mándi, Sándor Antus, Ana Martins, Attila Hunyadi, György Tibor Balogh, György Kalaus (†), Hedvig Bölcskei, László Hazai, and Tibor Kurtán
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absolute configuration ,Dracocephalum rupestre ,dracocephins A–B ,ECD calculation ,flavonoid alkaloids ,HPLC–ECD ,Science ,Organic chemistry ,QD241-441 - Abstract
Starting from racemic naringenin ((±)-1), a mixture of dracocephin A stereoisomers 6-(2”-pyrrolidinone-5”-yl)naringenin (±)-2a–d and its regioisomer, dracocephin B 8-(2”-pyrrolidinone-5”-yl)naringenin (±)-3a–d originally isolated from Dracocephalum rupestre, have been synthesized in a one-pot reaction. The separation of 2a–d and 3a–d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC–ECD measurements and TDDFT–ECD calculations. The synthesized flavonoid alkaloids were further characterized by physicochemical and in vitro pharmacological studies.
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- 2016
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15. Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291
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Peng Zhang, Xiao-Ming Li, Xin-Xin Mao, Attila Mándi, Tibor Kurtán, and Bin-Gui Wang
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bisindolyl benzenoid derivatives ,cytotoxicity ,marine alga-derived fungus ,Paecilomyces variotii ,TDDFT-ECD calculation ,Science ,Organic chemistry ,QD241-441 - Abstract
A new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative, varioloid A (1), was isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. Its structure was elucidated on the basis of extensive analysis of 1D and 2D NMR data and the absolute configuration was determined by time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. A similar compound, whose planar structure was previously described but the relative and absolute configurations and 13C NMR data were not reported, was also identified and was tentatively named as varioloid B (2). Both compounds 1 and 2 exhibited cytotoxicity against A549, HCT116, and HepG2 cell lines, with IC50 values ranging from 2.6 to 8.2 µg/mL.
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- 2016
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16. Synthesis and HPLC-ECD Study of Cytostatic Condensed O,N-Heterocycles Obtained from 3-Aminoflavanones
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Ádám Szappanos, Attila Mándi, Katalin Gulácsi, Erika Lisztes, Balázs István Tóth, Tamás Bíró, Anita Kónya-Ábrahám, Attila Kiss-Szikszai, Attila Bényei, Sándor Antus, and Tibor Kurtán
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neber rearrangement ,3-aminoflavanones ,antiproliferative activity ,TDDFT-ECD calculations ,HPLC-ECD ,3-(N-chloroacetylamino)-flavan-4-ol ,Microbiology ,QR1-502 - Abstract
Racemic chiral O,N-heterocycles containing 2-arylchroman or 2-aryl-2H-chromene subunit condensed with morpholine, thiazole, or pyrrole moieties at the C-3-C-4 bond were synthesized with various substitution patterns of the aryl group by the cyclization of cis- or trans-3-aminoflavanone analogues. The 3-aminoflavanone precursors were obtained in a Neber rearrangement of oxime tosylates of flavanones, which provided the trans diastereomer as the major product and enabled the isolation of both the cis- and trans-diastereomers. The cis- and trans-aminoflavanones were utilized to prepare three diastereomers of 5-aryl-chromeno[4,3-b][1,4]oxazines. Antiproliferative activity of the condensed heterocycles and precursors was evaluated against A2780 and WM35 cancer cell lines. For a 3-(N-chloroacetylamino)-flavan-4-ol derivative, showing structural analogy with acyclic acid ceramidase inhibitors, 0.15 μM, 3.50 μM, and 6.06 μM IC50 values were measured against A2780, WM35, and HaCat cell lines, and apoptotic mechanism was confirmed. Low micromolar IC50 values down to 2.14 μM were identified for the thiazole- and pyrrole-condensed 2H-chromene derivatives. Enantiomers of the condensed heterocycles were separated by HPLC using chiral stationary phase, HPLC-ECD spectra were recorded and TDDFT-ECD calculations were performed to determine the absolute configuration and solution conformation. Characteristic ECD transitions of the separated enantiomers were correlated with the absolute configuration and effect of substitution pattern on the HPLC elution order was determined.
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- 2020
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17. [1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines
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Dóra Szalóki Vargáné, László Tóth, Balázs Buglyó, Attila Kiss-Szikszai, Attila Mándi, Péter Mátyus, Sándor Antus, Yinghan Chen, Dehai Li, Lingxue Tao, Haiyan Zhang, and Tibor Kurtán
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domino knoevenagel-[1,5]-hydride shift-cyclization ,1,4-benzoxazepine ,1,5-benzoxazepine ,tddft-ecd calculation ,acetylcholinesterase inhibitory activity ,Organic chemistry ,QD241-441 - Abstract
Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 μM IC50 value.
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- 2020
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18. Peniciadametizine A, a Dithiodiketopiperazine with a Unique Spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] Skeleton, and a Related Analogue, Peniciadametizine B, from the Marine Sponge-Derived Fungus Penicillium adametzioides
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Yang Liu, Attila Mándi, Xiao-Ming Li, Ling-Hong Meng, Tibor Kurtán, and Bin-Gui Wang
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marine sponge ,endophytic fungus ,Penicillium adametzioides ,secondary metabolites ,antifungal activity ,Biology (General) ,QH301-705.5 - Abstract
Peniciadametizine A (1); a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2); as well as two known compounds, brasiliamide A (3); and viridicatumtoxin (4), were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT) conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD) calculations. The spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.
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- 2015
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19. Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction
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László Tóth, Yan Fu, Hai Yan Zhang, Attila Mándi, Katalin E. Kövér, Tünde-Zita Illyés, Attila Kiss-Szikszai, Balázs Balogh, Tibor Kurtán, Sándor Antus, and Péter Mátyus
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1,4-benzoxazepine ,diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization ,neuroprotective ,tert-amino effect ,TDDFT-ECD calculation ,Science ,Organic chemistry ,QD241-441 - Abstract
Condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties were prepared by a regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of 3JH,H coupling data with the geometry of major conformers accessed by DFT conformational analysis. Separated enantiomers of the products were characterized by HPLC-ECD data, which allowed their configurational assignment on the basis of TDDFT-ECD calculation of the solution conformers. Two compounds showed neuroprotective activities against hydrogen peroxide (H2O2) or β-amyloid25–35 (Aβ25–35)-induced cellular injuries in human neuroblastoma SH-SY5Y cells in the range of those of positive controls.
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- 2014
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20. Correction: Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291
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Peng Zhang, Xiao-Ming Li, Xin-Xin Mao, Attila Mándi, Tibor Kurtán, and Bin-Gui Wang
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bisindolyl benzenoid derivatives ,cytotoxicity ,marine alga-derived fungus ,Paecilomyces variotii ,TDDFT-ECD calculation ,Science ,Organic chemistry ,QD241-441 - Published
- 2018
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21. Lactones from the Sponge-Derived Fungus Talaromyces rugulosus
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Lisa Küppers, Weaam Ebrahim, Mona El-Neketi, Ferhat C. Özkaya, Attila Mándi, Tibor Kurtán, Raha S. Orfali, Werner E. G. Müller, Rudolf Hartmann, Wenhan Lin, Weiguo Song, Zhen Liu, and Peter Proksch
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Talaromyces rugulosus ,lactones ,ECD calculation ,cytotoxicity ,Biology (General) ,QH301-705.5 - Abstract
The marine-derived fungus Talaromyces rugulosus isolated from the Mediterranean sponge Axinella cannabina and cultured on solid rice medium yielded seventeen lactone derivatives including five butenolides (1–5), seven (3S)-resorcylide derivatives (6–12), two butenolide-resorcylide dimers (13 and 14), and three dihydroisocoumarins (15–17). Among them, fourteen compounds (1–3, 6–16) are new natural products. The structures of the isolated compounds were elucidated by 1D and 2D NMR (Nuclear Magnetic Resonance) spectroscopy as well as by ESI-HRMS (ElectroSpray Ionization-High Resolution Mass Spectrometry). TDDFT-ECD (Time-Dependent Density Functional Theory-Electronic Circular Dichroism) calculations were performed to determine the absolute configurations of chiral compounds. The butenolide-resorcylide dimers talarodilactones A and B (13 and 14) exhibited potent cytotoxicity against the L5178Y murine lymphoma cell line with IC50 values of 3.9 and 1.3 µM, respectively.
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- 2017
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22. Glucopyranosylidene-Spiro-Thiazolinones: Synthetic Studies and Determination of Absolute Configuration by TDDFT-ECD Calculations
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Katalin E. Szabó, Sándor Kun, Attila Mándi, Tibor Kurtán, and László Somsák
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spiro compound ,thiazolinone ,glucose derivative ,TDDFT-ECD ,Organic chemistry ,QD241-441 - Abstract
Reactions of O-peracylated C-(1-bromo-β-d-glucopyranosyl)formamides with thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one. While O-debenzoylations under a variety of conditions resulted in decomposition, during O-deacetylations the addition of MeOH to the thiazolinone moiety was observed, and with EtOH and water similar adducts were isolated or detected. The structure and stereochemistry of the new compounds were established by means of NMR and electronic circular dichroism (ECD) data supported by time-dependent density functional theory ECD (TDDFT-ECD) calculations. TDDFT-ECD calculations could efficiently distinguish the proposed epimeric products having different absolute configuration in the spiro heterocyclic ring.
- Published
- 2017
- Full Text
- View/download PDF
23. Isolation and characterization of three pairs of verrucosidin epimers from the marine sediment-derived fungus Penicillium cyclopium and configuration revision of penicyrone A and related analogues
- Author
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Yan-He Li, Attila Mándi, Hong-Lei Li, Xiao-Ming Li, Xin Li, Ling-Hong Meng, Sui-Qun Yang, Xiao-Shan Shi, Tibor Kurtán, and Bin-Gui Wang
- Subjects
Aquatic Science ,Oceanography ,Ecology, Evolution, Behavior and Systematics ,Biotechnology - Abstract
Verrucosidins, a methylated α-pyrone class of polyketides rarely reported upon, have been implicated in one or more neurological diseases. Despite the significance of verrucosidins as neurotoxins, the absolute configurations of most of the derivatives have not been accurately characterized yet. In this study, three pairs of C-9 epimeric verrucosidin derivatives, including the known compounds penicyrones A and B (1a/1b) and 9-O-methylpenicyrones A and B (2a/2b), the new compounds 9-O-ethylpenicyrones A and B (3a/3b), together with the related known derivative verrucosidin (4), were isolated and identified from the culture extract of Penicillium cyclopium SD-413, which was obtained from the marine sediment collected from the East China sea. Their structures were established based on an in-depth analysis of nuclear magnetic resonances (NMR) and mass spectroscopic data. Determination of the absolute configurations of these compounds was accomplished by Mosher’s method and time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) and optical rotation (OR). The configurational assignment of penicyrone A demonstrated that the previously reported C-6 absolute configuration of verrucosidin derivatives needs to be revised from (6S) to (6R). The 9R/9S epimers of compounds 1–3 were found to exhibit growth inhibition against some pathogenic bacteria, indicating that they have potential as lead compounds for the creation of antimicrobial agents.
- Published
- 2023
24. Zizaane-Type Sesquiterpenoids and Their Rearranged Derivatives from Agarwood of an Aquilaria Plant
- Author
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Jing-Zhe Yuan, Yi-Ling Yang, Wei Li, Li Yang, Hao-Fu Dai, Attila Mándi, Cai-Hong Cai, Hui-Qin Chen, Wen-Hua Dong, Tibor Kurtán, Wen-Li Mei, and Hao Wang
- Subjects
Magnetic Resonance Spectroscopy ,zizaane ,Chemical Phenomena ,Cell Survival ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Organic chemistry ,Article ,Analytical Chemistry ,Mice ,QD241-441 ,TDDFT-ECD ,Drug Discovery ,Animals ,Physical and Theoretical Chemistry ,agarwood ,Aquilaria sp ,sesquiterpenoid ,anti-inflammatory effect ,Molecular Structure ,Wood ,RAW 264.7 Cells ,Chemistry (miscellaneous) ,Thymelaeaceae ,Molecular Medicine ,Sesquiterpenes - Abstract
Nine new sesquiterpenoids (1–9) were isolated from ethyl ether extract of agarwood originated from Aquilaria sp., including three novel sesquiterpenoids (1–3) derived from zizaane, together with six zizaane-type sesquiterpenoids (4–9). All structures were unambiguously elucidated based on 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of sesquiterpenoids was determined by comparison of the experimental and computed ECD spectra. In vitro anti-inflammatory assessment showed that compound 9 exhibited inhibition of NO production in LPS-stimulated RAW264.7 cells with an IC50 value of 62.22 ± 1.27 μM.
- Published
- 2022
25. Discovery of benthol A and its challenging stereochemical assignment: opening up a new window for skeletal diversity of super-carbon-chain compounds
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Yi Yu, Attila Mándi, Jiao-Yang Luo, Jun Wu, Tibor Kurtán, Zhong-Ping Jiang, Shi-Hao Sun, Meihua Yang, Li Shen, and Wen-Hua Chen
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Carbon chain ,chemistry.chemical_classification ,Ozonolysis ,Double bond ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Absolute configuration ,Backbone chain ,Ether ,General Chemistry ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Stereocenter ,chemistry.chemical_compound ,Molecule - Abstract
Super-carbon-chain compounds (SCCCs) are marine organic molecules featuring long polyol carbon chains with numerous stereocenters. Polyol–polyene compounds (PPCs) and ladder-frame polyethers (LFPs) are two major families. It is highly challenging to establish the absolute configurations of SCCCs. In this century, few new SCCC families have been reported. Benthol A, an aberrant SCCC, was obtained from a South China Sea benthic dinoflagellate that should belong to a new taxon. Its planar structure and absolute configuration, containing thirty-five carbon stereocenters, were unambiguously established by a combination of extensive NMR spectroscopic investigations, periodate degradation of the 1,2-diol groups, ozonolysis of the carbon–carbon double bonds, J-based configurational analysis, NOE interactions, modified Mosher's MTPA ester method, and DFT-NMR 13C chemical-shift calculations aided by DP4+ statistical analysis. Benthol A displayed potent antimalarial activity against Plasmodium falciparum 3D7 parasites. This new molecule combines extraordinary structural features, particularly eight scattered ether rings on a C72 backbone chain, which places it within a new SCCC family between PPCs and LFPs, herein termed polyol–polyether compounds. This suggestion was strongly supported by principal component analysis. The discovery of benthol A does not only provide new insights into the untapped biosynthetic potential of marine dinoflagellates, but also opens up a new window for skeletal diversity of SCCCs., The discovery of benthol A, a marine natural product featuring thirty-five carbon stereocenters and eight scattered ether rings within a C72 backbone chain, inaugurates a new family of super-carbon-chain compounds.
- Published
- 2021
26. Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the α/β-fold epoxide hydrolase Alp1U
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Attila Mándi, Bidhan Chandra De, Yiguang Zhu, Zhuangjie Fang, Changsheng Zhang, Li-Ping Zhang, Wenjun Zhang, Chunfang Yang, and Tibor Kurtán
- Subjects
Ethylene Oxide ,0301 basic medicine ,Stereochemistry ,Diol ,Epoxide ,Crystallography, X-Ray ,Biochemistry ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Nucleophile ,Epoxide hydrolase ,Molecular Biology ,Epoxide Hydrolases ,Sequence Homology, Amino Acid ,030102 biochemistry & molecular biology ,Chemistry ,Hydrolysis ,Regioselectivity ,Stereoisomerism ,Cell Biology ,Streptomyces ,Enzyme structure ,Protein Structure, Tertiary ,Kinetics ,030104 developmental biology ,Mutation ,Mutagenesis, Site-Directed ,Enzymology ,Epoxy Compounds ,Oxyanion hole - Abstract
Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.
- Published
- 2020
27. Regio‐ and Stereoselective Synthesis of Benzoquinolizidines
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Anna Alekszi‐Kaszás, Klára Käfer‐Beke, Tamás R. Varga, Attila Bényei, Tibor Kovács, Attila Mándi, Tibor Kurtán, András Simon, and Péter Nemes
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General Chemistry - Published
- 2022
28. Oxidized Juncuenin B Analogues with Increased Antiproliferative Activity on Human Adherent Cell Lines: Semisynthesis and Biological Evaluation
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Tímea Gonda, Ágnes Kulmány, Andrea Vasas, Tibor Kurtán, Barbara Tóth, István Zupkó, Csaba Bús, Norbert Kúsz, Judit Hohmann, Attila Mándi, and Attila Hunyadi
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Stereochemistry ,Pharmaceutical Science ,01 natural sciences ,Article ,Analytical Chemistry ,HeLa ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Cell Adhesion ,Animals ,Humans ,Moiety ,Derivatization ,Density Functional Theory ,Alkyl ,Cell Proliferation ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Chemistry ,Spectrum Analysis ,Organic Chemistry ,biology.organism_classification ,Semisynthesis ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Complementary and alternative medicine ,Cell culture ,NIH 3T3 Cells ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Phenanthrenes ,Oxidation-Reduction ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Phenanthrenes have become the subject of intensive research during the past decades because of their structural diversity and wide range of pharmacological activities. Earlier studies demonstrated that semisynthetic derivatization of these natural compounds could result in more active agents, and oxidative transformations are particularly promising in this regard. In our work, a natural phenanthrene, juncuenin B, was transformed by hypervalent iodine(III) reagents using a diversity-oriented approach. Eleven racemic semisynthetic compounds were produced, the majority containing an alkyl substituted p-quinol ring. Purification of the compounds was carried out by chromatographic techniques, and their structures were elucidated by 1D and 2D NMR spectroscopic methods. Stereoisomers of the bioactive derivatives were separated by chiral-phase HPLC and the absolute configurations of the active compounds, 2,6-dioxo-1,8a-dimethoxy-1,7-dimethyl-8-vinyl-9,10-dihydrophenanthrenes (1a–d), and 8a-ethoxy-1,7-dimethyl-6-oxo-8-vinyl-9,10-dihydrophenanthrene-2-ols (7a,b) were determined by ECD measurements and TDDFT-ECD calculations. The antiproliferative activities of the compounds were tested on different (MCF-7, T47D, HeLa, SiHa, C33A, A2780) human gynecological cancer cell lines. Compounds 1a–d, 4a, 6a, and 7a possessed higher activity than juncuenin B on several tumor cell lines. The structure–activity relationship studies suggested that the p-quinol (2,5-cyclohexadien-4-hydroxy-1-one) moiety has a considerable effect on the antiproliferative properties, and substantial differences could be identified in the activities of the stereoisomers.
- Published
- 2020
29. An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways
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Sándor Antus, Ling xue Tao, Dóra Szalóki, Attila Mándi, Ding Xun, T. Kovacs, Sha sha Ji, Hai-Yan Zhang, and Tibor Kurtán
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,MAP Kinase Signaling System ,p38 mitogen-activated protein kinases ,Apoptosis ,Pharmacology ,medicine.disease_cause ,Neuroprotection ,Article ,Rats, Sprague-Dawley ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Benzopyrans ,Pharmacology (medical) ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Neurons ,Chemistry ,Stereoisomerism ,Free Radical Scavengers ,Hydrogen Peroxide ,General Medicine ,Oxidative Stress ,Neuroprotective Agents ,030104 developmental biology ,030220 oncology & carcinogenesis ,Phosphorylation ,Proto-Oncogene Proteins c-akt ,Oxidative stress - Abstract
Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1–10 μM) concentration-dependently prevented H(2)O(2)-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H(2)O(2)-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 μM) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate.
- Published
- 2020
30. Furoic acid derivatives from the endophytic fungus Coniothyrium sp
- Author
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Zhen Liu, Sándor Balázs Király, Tibor Kurtán, Attila Mándi, Nam Michael Tran-Cong, Wenhan Lin, and Peter Proksch
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Models, Molecular ,Circular dichroism ,Stereochemistry ,Molecular Conformation ,Antineoplastic Agents ,010402 general chemistry ,Mass spectrometry ,01 natural sciences ,Catalysis ,Analytical Chemistry ,Mice ,Ascomycota ,Cell Line, Tumor ,Drug Discovery ,Animals ,Sigma bond ,Furans ,Spectroscopy ,Pharmacology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Absolute configuration ,Stereoisomerism ,Chromophore ,0104 chemical sciences ,Fermentation ,Enantiomer ,Chirality (chemistry) - Abstract
The endophytic fungus Coniothyrium sp. was isolated from leaves of Quercus robur. Fermentation of this fungus on solid rice medium yielded two new furoic acid derivatives (1 and 2) and two additional known compounds. The structures of the new compounds were determined by extensive analysis of 1D and 2D nuclear magnetic resonance spectra as well as high-resolution mass spectrometry data. Compound 1, containing three aromatic chromophores attached by rotatable sigma bonds and a chirality center in benzylic position, was found to be a scalemic mixture with an excess of the (S) enantiomer, the absolute configuration of which was elucidated as by the solution time-dependent density functional theory-electronic circular dichroism approach. The ωB97X/TZVP PCM/MeCN and SOGGA11-X/TZVP SMD/MeCN methods were used for geometry reoptimization to reproduce the solution conformational ensemble. All isolated compounds were tested for their cytotoxicity but proved to be inactive.
- Published
- 2020
31. Pigments of the Moss Paraleucobryum longifolium: Isolation and Structure Elucidation of Prenyl-Substituted 8,8′-Linked 9,10-Phenanthrenequinone Dimers
- Author
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Dezső Csupor, Tibor Kurtán, Martin Vollár, Norbert Kúsz, Katalin E. Kövér, Attila Mándi, Péter Szűcs, Marianna Marschall, Seyyed A. Senobar Tahaei, István Zupkó, and Judit Hohmann
- Subjects
Pharmacology ,Complementary and alternative medicine ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Article ,Analytical Chemistry - Abstract
In a search for new secondary metabolites from mosses, leucobryns A–E, axially chiral 9,10-phenanthrenequinone dimers, were isolated from Paraleucobryum longifolium (1–5), together with diosmetin triglycoside. Leucobryns B (2) and C (3) were proved to be homodimeric atropodiastereomers containing both axial and central chirality elements, while leucobryns D (4) and E (5) were found to be heterodimeric atropodiastereomers containing central chirality in only one of the two monomeric units. Axial chirality of the compounds was determined by ECD measurements and sTDA ECD calculations, while the central chirality elements were assigned by TDDFT-SOR calculations. Leucobryns represent the first 9,10-phenanthrenequinone dimers, the monomers of which are linked through their C-8 atoms. Leucobryns B–E contain an uncommon C10 monoterpenoid side chain, in which isoprenoid units are joined by 3,4 linkages. Leucobryns A and B exhibited weak antiproliferative activity against several human cancer cell lines.
- Published
- 2020
32. Induction of Secondary Metabolites from the Marine-Derived Fungus Aspergillus versicolor through Co-cultivation with Bacillus subtilis
- Author
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Zhen Liu, Sebastian Scharf, Mohamed Kamel, Ferhat Can Özkaya, Attila Mándi, Mostafa A. Fouad, Tibor Kurtán, Nada M. Abdel-Wahab, Georgios Daletos, Peter Proksch, Weaam Ebrahim, Wenhan Lin, Werner E.G. Müller, and Rainer Kalscheuer
- Subjects
Circular dichroism ,Magnetic Resonance Spectroscopy ,Stereochemistry ,Pharmaceutical Science ,Anthraquinones ,Microbial Sensitivity Tests ,Bacillus subtilis ,Quinolones ,Gram-Positive Bacteria ,Peptides, Cyclic ,Mass Spectrometry ,Analytical Chemistry ,Mice ,chemistry.chemical_compound ,Természettudományok ,Cell Line, Tumor ,Drug Discovery ,Animals ,Kémiai tudományok ,Axenic ,Pharmacology ,Dose-Response Relationship, Drug ,biology ,Cytotoxins ,Chemistry ,Circular Dichroism ,Organic Chemistry ,Absolute configuration ,biology.organism_classification ,Coculture Techniques ,Anti-Bacterial Agents ,Aspergillus ,Complementary and alternative medicine ,Molecular Medicine ,Aspergillus versicolor ,Antibacterial activity ,Bacteria - Abstract
A new cyclic pentapeptide, cotteslosin C (1), a new aflaquinolone, 22-epi-aflaquinolone B (3), and two new anthraquinones (9 and 10), along with thirty known compounds (2, 4 – 8, 11 – 34) were isolated from a co-culture of the sponge-associated fungus Aspergillus versicolor with Bacillus subtilis. The new metabolites were only detected in the co-culture extract, but not when the fungus was grown under axenic conditions. Furthermore, the co-culture extract exhibited an enhanced accumulation of the known constituents versicolorin B (14), averufin (16), and sterigmatocyctin (19) by factors of 1.5, 2.0, and 4.7, respectively, compared to the axenic fungal culture. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and mass spectrometry as well as by comparison with literature data. The absolute configuration of compounds 3, 9, and 10 was determined by ECD (electronic circular dichroism) analysis aided by TDDFT-ECD (time-dependent density functional theory electronic circular dichroism) calculations. Compounds 15, 18 – 21, and 26 exhibited strong to moderate cytotoxic activity against the mouse lymphoma cell line L5178Y, with IC50 values ranging from 2.0 to 21.2 µM, while compounds 14, 16, 31, 32, and 33 displayed moderate inhibitory activities against several gram-positive bacteria, with MIC values ranging from 12.5 to 50 µM.
- Published
- 2019
33. Induction of cryptic metabolites of the endophytic fungus Trichocladium sp. through OSMAC and co-cultivation
- Author
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Zhen Liu, Attila Mándi, Tibor Kurtán, Wenhan Lin, Werner E.G. Müller, Rainer Kalscheuer, Peter Proksch, and Nam Michael Tran-Cong
- Subjects
biology ,Stereochemistry ,General Chemical Engineering ,Tryptophan ,02 engineering and technology ,General Chemistry ,Fungus ,Bacillus subtilis ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Sesquiterpene ,01 natural sciences ,0104 chemical sciences ,Houttuynia cordata ,chemistry.chemical_compound ,chemistry ,Cell culture ,0210 nano-technology ,Axenic ,Derivative (chemistry) - Abstract
The endophytic fungus Trichocladium sp. isolated from roots of Houttuynia cordata was cultured on solid rice medium, yielding a new amidepsine derivative (1) and a new reduced spiro azaphilone derivative (3) together with eight known compounds (4–11). Co-cultivation of Trichocladium sp. with Bacillus subtilis resulted in induction of a further new compound (2) and a 10-fold increase of 11 compared to the axenic fungal culture. Moreover, when the fungus was cultivated on peas instead of rice, a new sesquiterpene derivative (13) and two known compounds (12 and 14) were obtained. Addition of 2% tryptophan to rice medium led to the isolation of a new bismacrolactone (15). The structures of the new compounds were elucidated by HRESIMS, 1D and 2D NMR as well as by comparison with the literature. A combination of TDDFT-ECD, TDDFT-SOR, DFT-VCD and DFT-NMR calculations were applied to determine the absolute and relative configurations of 13 and 15. Compounds 7, 11 and 15 exhibited strong cytotoxicity against the L5178Y mouse lymphoma cell line with IC50 values of 0.3, 0.5 and 0.2 μM, respectively.
- Published
- 2019
34. Expanding the chemical diversity of an endophytic fungus Bulgaria inquinans, an ascomycete associated with mistletoe, through an OSMAC approach
- Author
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Elena Ancheeva, Ni Putu Ariantari, Tibor Kurtán, Attila Mándi, Werner E.G. Müller, Georgios Daletos, Wenhan Lin, and Peter Proksch
- Subjects
biology ,Strain (chemistry) ,Stereochemistry ,Chemistry ,General Chemical Engineering ,Absolute configuration ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Bulgaria inquinans ,Viscum album ,Moiety ,Fermentation ,Enantiomer ,0210 nano-technology ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
An endophytic fungus Bulgaria inquinans (isolate MSp3-1), isolated from mistletoe (Viscum album), was subjected to fermentation on solid Czapek medium. Chromatographic workup of the crude EtOAc extract yielded five new natural products (1–5). Subsequent application of the “One Strain, MAny Compounds” (OSMAC) strategy on this strain by the addition of a mixture of salts (MgSO4, NaNO3 and NaCl) to solid Czapek medium induced the accumulation of nine additional new secondary metabolites (6–13, 16), with most of them (8, 10–12) not detectable in cultures lacking the salt mixture. The structures of the new compounds were established on the basis of the 1D/2D NMR and HRESIMS data. The TDDFT-ECD method was applied to determine the absolute configurations of the new compounds 1, 4 and 6 as well as of the previously reported bulgarialactone B (14), for which the absolute configuration was unknown so far. The modified Mosher's method was performed to assign the absolute configurations of 12 and 13. TDDFT-ECD analysis also allowed determining the absolute configuration of (+)-epicocconone, which had an enantiomeric absolute configuration in the tricyclic moiety compared to that of bulgarialactone B (14). All the isolated metabolites were evaluated for their cytotoxic activity. Compound 2 was found to possess strong cytotoxic activity against the murine lymphoma cell line L5178Y with an IC50 value of 1.8 μM, while the remaining metabolites were shown to be inactive.
- Published
- 2019
35. Granatripodins A-B, limonoids featuring a Tricyclo[3.3.1.0
- Author
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Li, Shen, Xiao-Peng, Zou, Wan-Shan, Li, Attila, Mándi, Tibor, Kurtán, and Jun, Wu
- Subjects
Limonins ,Structure-Activity Relationship ,Dose-Response Relationship, Drug ,Seeds ,Molecular Conformation ,Pregnane X Receptor ,Humans ,Meliaceae - Abstract
Two unprecedented limonoids incorporating a sterically encumbered cyclopropane ring, named granatripodins A (1) and B (2), featuring the presence of a tricyclo[3.3.1.0
- Published
- 2021
36. Induction of New Lactam Derivatives From the Endophytic Fungus Aplosporella javeedii Through an OSMAC Approach
- Author
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Sebastian Wesselborg, Kun Zou, Zhen Liu, Zhiyong Guo, Fabian Stuhldreier, Tibor Kurtán, Laura Schmitt, Attila Mándi, Peter Proksch, and Ying Gao
- Subjects
Microbiology (medical) ,Stereochemistry ,lcsh:QR1-502 ,Fungus ,OSMAC approach ,Microbiology ,Jurkat cells ,lcsh:Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,TDDFT-ECD ,lactam derivatives ,Cytotoxicity ,030304 developmental biology ,0303 health sciences ,biology ,030306 microbiology ,Absolute configuration ,Aplosporella javeedii ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,DFT-NMR ,chemistry ,Apoptosis ,Lactam ,Fermentation ,OR calculations - Abstract
Fermentation of the endophytic fungus Aplosporella javeedii on solid rice medium in presence of either 3.5% NaNO3 or 3.5% monosodium glutamate caused a significant change of the fungal metabolite pattern compared to fungal controls grown only on rice. Chemical investigation of the former fungal extracts yielded 11 new lactam derivatives, aplosporellins A–K (2–12), in addition to the known compound, pramanicin A (1). All of these compounds were not detected when the fungus was grown on rice medium without these activators thereby indicating the power of this OSMAC approach. The structures of the new compounds were elucidated by one- and two- dimensional NMR spectroscopy, DFT-NMR calculations and by mass spectrometry as well as by comparison with the literature whereas the absolute configuration of the lactam core was determined by TDDFT-ECD and OR calculations. Pramanicin A (1) showed strong cytotoxicity against human lymphoma (Ramos) and leukemia (Jurkat J16) cells with IC50 values of 4.7 and 4.4 μM, respectively. Mechanistic studies indicated that 1 activates caspase-3 and induces apoptotic cell death.
- Published
- 2020
37. TDDFT-ECD and DFT-NMR studies of thaigranatins A-E and granatumin L isolated from
- Author
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Attila, Mándi, Jun, Wu, and Tibor, Kurtán
- Abstract
TDDFT-ECD calculations were utilized to explain the mirror image or different ECD spectra of previously reported homochiral natural products thaigranatins A-E and granatumin L, the simple comparison of which would result in a wrong stereochemical conclusion. The configurational assignment was confirmed independently and geometrical parameters of the chromophores governing the ECD spectra were identified in the structurally related natural products by analyzing the ECD spectra and geometries of the low-energy computed conformers obtained by different methods. Different conformations of the furan-2-yl-δ-lactone subunit were found responsible for the mirror image ECD spectra of the homochiral thaigranatins C-E. Two DFT
- Published
- 2020
38. Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches
- Author
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Zhen Liu, Peter Proksch, Tibor Kurtán, Mohamed Kamel, Mostafa A. Fouad, Miada F. Abdelwahab, Georgios Daletos, Weaam Ebrahim, Werner E.G. Müller, and Attila Mándi
- Subjects
Circular dichroism ,biology ,010405 organic chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Ethyl acetate ,Diastereomer ,Bacillus subtilis ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Természettudományok ,Drug Discovery ,Aspergillus versicolor ,Epimer ,Kémiai tudományok ,Conformational isomerism - Abstract
Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A (1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3–8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium. When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9–11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blue-shifted overlapping n-π∗ ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.
- Published
- 2018
39. Structural, stereochemical, and bioactive studies of cembranoids from Chinese soft coral Sarcophyton trocheliophorum
- Author
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Li Gong Yao, Tibor Kurtán, Jia Li, Yue-Wei Guo, Le Fu Lan, Attila Mándi, and Lin Fu Liang
- Subjects
010405 organic chemistry ,Chemistry ,Stereochemistry ,Coral ,Organic Chemistry ,Absolute configuration ,Time-dependent density functional theory ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Nmr data ,0104 chemical sciences ,chemistry.chemical_compound ,Természettudományok ,Drug Discovery ,Sarcophyton trocheliophorum ,Moiety ,Specific rotation ,Kémiai tudományok ,Antibacterial activity - Abstract
A series of highly oxidative new cembranoids with diverse structural features such as a dienoate moiety (sarcophytonolides S – U, 1–3) or an α,β-unsaturated e-lactone (sartrolides H – J, 4–6) were obtained from Hainan soft coral Sarcophyton trocheliophorum, along with known related analogues 7–13. It is an extremely challenging work to determine the absolute configurations of these metabolites. For compounds 1, 3 and 4, solution TDDFT calculation of ECD and specific rotation were applied in combination with conformational analysis and NMR data to determine their relative and absolute configurations, leading to the revision of relative configuration of 14. The absolute configurations of compounds 8–10 were determined by the solid-state TDDFT-ECD approach, and that of 8 was further confirmed by single-crystal X-ray diffraction experiment with Cu Kα radiation. In the bioassays, compound 8 exhibited not only moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC50 = 15.4 μM) but also moderate antibacterial activity against Staphylococcus aureus Newman strain (MIC50 = 250 μM).
- Published
- 2018
40. Granatripodins A–B, limonoids featuring a Tricyclo[3.3.1.02,8]nonane motif: Absolute configuration and agonistic effects on human pregnane–X–receptor
- Author
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Attila Mándi, Jun Wu, Wan-Shan Li, Tibor Kurtán, Li Shen, and Xiao-Peng Zou
- Subjects
Steric effects ,biology ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Absolute configuration ,biology.organism_classification ,Ring (chemistry) ,Limonoid ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Cyclopropane ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Cascade reaction ,chemistry ,Xylocarpus granatum ,Drug Discovery ,medicine ,Nonane ,Molecular Biology ,medicine.drug - Abstract
Two unprecedented limonoids incorporating a sterically encumbered cyclopropane ring, named granatripodins A (1) and B (2), featuring the presence of a tricyclo[3.3.1.02,8]nonane motif, were obtained from seeds of the Thai Xylocarpus granatum. The planar structures and absolute configurations of these limonoids were unambiguously established by NMR investigations, TDDFT-ECD and DFT-NMR calculations, and single-crystal X-ray diffraction analysis (Cu Kα). Most notably, granatripodin A (1) exhibited agonistic effects on human pregnane–X–receptor at the concentration of 100.0 nM. The biosynthetic origins of these limonoids via a radical cascade reaction are proposed. This study exemplifies a universal approach for the stereochemical assignment of polycyclic compounds with a cyclopropane-embedded cage scaffold.
- Published
- 2021
41. Cytotoxic labdane diterpenes and bisflavonoid atropisomers from leaves of Araucaria bidwillii
- Author
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Werner E.G. Müller, Abdel Nasser B. Singab, Aya N. Talaat, Peter Proksch, Rola M. Labib, Sherif S. Ebada, Tibor Kurtán, and Attila Mándi
- Subjects
Atropisomer ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Ether ,Araucaria bidwillii ,010402 general chemistry ,Antimicrobial ,01 natural sciences ,Biochemistry ,food.food ,0104 chemical sciences ,Labdane ,chemistry.chemical_compound ,food ,Természettudományok ,chemistry ,Drug Discovery ,Organic chemistry ,Phloretic acid ,Diterpene ,Kémiai tudományok ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Chemical investigation of a methanolic extract of leaves from Araucaria bidwillii (Araucariaceae) from Egypt afforded four new labdane diterpenoidal metabolites (1–4) together with one known diterpene, 7-oxocallitrisic acid (5), two triterpenoidal metabolites, 2-O-acetyl-11-keto-boswellic acid (6) and β-sitosterol-3-O-glucopyranoside (7), phloretic acid (8), and two methylated bisflavonoids, agathisflavone-4′,7,7″-trimethyl ether (9) and cupressuflavone-4′,7,7″-trimethyl ether (10). The new metabolites 1–4 were unambiguously identified by applying extensive 1D and 2D NMR spectroscopic studies as well as HRESIMS. The relative and absolute configurations of 1–4 were determined using ROESY and the modified Mosher's method, respectively. All isolated compounds were assessed for their antimicrobial, antitubercular and cytotoxic activities. Among the tested compounds, the new labdane diterpenes 1–4 revealed significant cytotoxic activity against mouse lymphoma L5178Y cell line with IC50 values ranging from 1.4 to 12.9 μM, respectively.
- Published
- 2017
42. Hydroquinone derivatives from the marine-derived fungus Gliomastix sp
- Author
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Mohamed S. Elnaggar, Tibor Kurtán, Werner E.G. Müller, Rainer Kalscheuer, Peter Proksch, Attila Mándi, Abdel Nasser B. Singab, Wenhan Lin, Weaam Ebrahim, and Zhen Liu
- Subjects
biology ,Hydroquinone ,010405 organic chemistry ,Stereochemistry ,General Chemical Engineering ,Alkaloid ,Gliomastix ,General Chemistry ,Fungus ,biology.organism_classification ,01 natural sciences ,0104 chemical sciences ,Mycobacterium tuberculosis ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Természettudományok ,chemistry ,Ic50 values ,Kémiai tudományok ,Cytotoxicity ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Eight new hydroquinone derivatives, gliomastins A–D (1–4), 9-O-methylgliomastin C (5), acremonin A 1-O-β-D-glucopyranoside (6), gliomastin E 1-O-β-D-glucopyranoside (7), and 6′-O-acetyl-isohomoarbutin (8), together with seven known analogues were isolated from the marine-derived fungus Gliomastix sp. Their structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR measurements aided by DFT NMR calculations as well as MS data. TDDFT-ECD and OR calculations were performed to determine the absolute configurations of 1 and the aglycones of 6 and 7. Compound 1 features a novel skeleton, biogenetically derived from a Diels–Alder reaction between derivatives of 11 and 13. Compound 2 represents a rare sulfur-containing alkaloid derived from the known hydroquinone 13. Compounds 1, 10 and 12 showed strong cytotoxicity against the L5178Y mouse lymphoma cell line with IC50 values of 1.8, 1.0 and 1.1 μM, respectively. Compound 3 exhibited moderate antitubercular activity against Mycobacterium tuberculosis with a MIC value of 12.5 μM.
- Published
- 2017
43. Induction of cryptic metabolites of the endophytic fungus
- Author
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Nam Michael, Tran-Cong, Attila, Mándi, Tibor, Kurtán, Werner E G, Müller, Rainer, Kalscheuer, Wenhan, Lin, Zhen, Liu, and Peter, Proksch
- Abstract
The endophytic fungus
- Published
- 2019
44. Expanding the chemical diversity of an endophytic fungus
- Author
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Ni P, Ariantari, Georgios, Daletos, Attila, Mándi, Tibor, Kurtán, Werner E G, Müller, Wenhan, Lin, Elena, Ancheeva, and Peter, Proksch
- Abstract
An endophytic fungus
- Published
- 2019
45. Xylomolones A-D from the Thai Mangrove Xylocarpus moluccensis: Assignment of Absolute Stereostructures and Unveiling a Convergent Strategy for Limonoid Biosynthesis
- Author
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Jun Wu, Junjun Liu, Li Shen, Attila Mándi, Wan-Shan Li, and Tibor Kurtán
- Subjects
Limonins ,Circular dichroism ,biology ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Xylocarpus ,Xylocarpus moluccensis ,Stereoisomerism ,Carbon-13 NMR ,010402 general chemistry ,biology.organism_classification ,Limonoid ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Biosynthesis ,chemistry ,medicine ,Density functional theory ,Meliaceae ,Nuclear Magnetic Resonance, Biomolecular ,medicine.drug - Abstract
Two new 9,10- seco limonoids with a central 3,4-dihydro-2 H-pyran motif, named xylomolones A and B (1 and 2, respectively), possessing identical absolute configurations but reversed alignments of ring A, compared to the tricyclic core of rings B-D, were obtained from seeds of the Thai mangrove Xylocarpus moluccensis, together with a highly modified 1,2- seco limonoid, named xylomolone C (3), containing a novel 3-oxabicyclo[3.2.1]octane-2,7-dione motif, and a new C11-terpenic acid methyl ester (4). The relative and absolute configurations of 1-4 were evidenced by extensive nuclear magnetic resonance (NMR) investigations combined with density functional theory and time-dependent density functional theory calculations of electronic circular dichroism, specific optical rotation, and 13C NMR data. The co-isolation of 1-4 allowed us to propose a novel convergent strategy for limonoid biosynthesis for the first time. This study demonstrates that mangroves of the genus Xylocarpus harbor new limonoid biosynthetic routes.
- Published
- 2019
46. Co-culture of the fungus Fusarium tricinctum with Streptomyces lividans induces production of cryptic naphthoquinone dimers
- Author
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Attila Mándi, Michele Bonus, Zhen Liu, Tibor Kurtán, Wenhan Lin, Mariam Moussa, Rudolf Hartmann, Weaam Ebrahim, Peter Proksch, Rainer Kalscheuer, and Holger Gohlke
- Subjects
Depsipeptide ,biology ,Stereochemistry ,General Chemical Engineering ,Absolute configuration ,Lipopeptide ,02 engineering and technology ,General Chemistry ,Fungus ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Földtudományok ,01 natural sciences ,Naphthoquinone ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Természettudományok ,ddc:540 ,0210 nano-technology ,Axenic ,Two-dimensional nuclear magnetic resonance spectroscopy ,Zearalenone - Abstract
Co-cultivation of the endophytic fungus Fusarium tricinctum with Streptomyces lividans on solid rice medium led to the production of four new naphthoquinone dimers, fusatricinones A–D (1–4), and a new lateropyrone derivative, dihydrolateropyrone (5), that were not detected in axenic fungal controls. In addition, four known cryptic compounds, zearalenone (7), (−)-citreoisocoumarin (8), macrocarpon C (9) and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (10), that were likewise undetectable in extracts from fungal controls, were obtained from the co-culture extracts. The known antibiotically active compound lateropyrone (6), the depsipeptides enniatins B (11), B1 (12) and A1 (13), and the lipopeptide fusaristatin A (14), that were present in axenic fungal controls and in co-culture extracts, were upregulated in the latter. The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The relative and absolute configuration of dihydrolateropyrone (5) was elucidated by TDDFT-ECD calculations.
- Published
- 2019
47. Co-culture of the fungus
- Author
-
Mariam, Moussa, Weaam, Ebrahim, Michele, Bonus, Holger, Gohlke, Attila, Mándi, Tibor, Kurtán, Rudolf, Hartmann, Rainer, Kalscheuer, Wenhan, Lin, Zhen, Liu, and Peter, Proksch
- Abstract
Co-cultivation of the endophytic fungus
- Published
- 2018
48. Separation and configurational assignment of stereoisomeric phenalenones from the marine mangrove-derived fungus Penicillium herquei MA-370
- Author
-
Attila Mándi, Bin-Gui Wang, Xin Li, Sui-Qun Yang, Sándor Balázs Király, Xiaoming Li, Hui Liu, and Tibor Kurtán
- Subjects
Stereochemistry ,Angiotensin-Converting Enzyme Inhibitors ,Fungus ,Peptidyl-Dipeptidase A ,01 natural sciences ,Biochemistry ,Structure-Activity Relationship ,Drug Discovery ,Binding site ,Molecular Biology ,Density Functional Theory ,Marine fungi ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Penicillium ,Absolute configuration ,Stereoisomerism ,Phenalenes ,Penicillium herquei ,biology.organism_classification ,0104 chemical sciences ,Chiral column chromatography ,010404 medicinal & biomolecular chemistry ,Enzyme ,Chirality (chemistry) - Abstract
Eight phenalenone derivatives, including four new compounds, aceneoherqueinones A and B (1 and 2), (+)-aceatrovenetinone A (3a), and (+)-aceatrovenetinone B (3d), along with four known congeners, (–)-aceatrovenetinone A (3b), (–)-aceatrovenetinone B (3c), (–)-scleroderolide (4a), and (+)-scleroderolide (4b), were characterized from the marine mangrove-derived fungus Penicillium herquei MA-370. Among them, compounds 1 and 2 are rare phenalenone derivatives featuring cyclic ether unit between C-5 and C-2′. All of these compounds were subjected to chiral HPLC analysis, and the unstable stereoisomers 3a–3d, containing configurationally labile chirality centers, were characterized by online HPLC-ECD measurements supported with TDDFT-ECD calculations. The structures of these compounds were elucidated by detailed analysis of their NMR and mass spectroscopic data, and the absolute configuration of compound 1 was confirmed by X-ray diffraction analysis, while those of compounds 2 and 3a–3d were determined by TDDFT-ECD calculations of their ECD spectra. All of the isolated compounds were tested for the inhibitory activity against angiotensin-I-converting enzyme (ACE), and compounds 1 and 2 displayed activity with IC50 values 3.10 and 11.28 μM, respectively. The intermolecular interaction and potential binding sites of 1 and 2 with ACE were elaborated by molecular docking, showing that compound 1 bound well with ACE via hydrogen interactions with residues Ala261, Gln618, Trp621, and Asn624, while compound 2 interacted with residues Asp358 and Tyr360.
- Published
- 2021
49. Synthesis ofC-2- andC-3-SulfonatomethylO- andS-Glycosides by Horner-Wadsworth-Emmons Olefination
- Author
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István Komáromi, Attila Mándi, Dániel Eszenyi, Mihály Herczeg, Attila Bényei, and Anikó Borbás
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Stereochemistry ,Organic Chemistry ,Glycoside ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Molecular dynamics ,chemistry ,Glucoside ,Nucleophilic substitution ,Moiety ,Physical and Theoretical Chemistry - Abstract
The applicability of the Horner–Wadsworth–Emmons olefination to the introduction of the sulfonatomethyl moiety at the 2- and 3-positions of orthogonally protected O- and S-glycosides has been studied. The conformational preferences and relative energies of the exo- and endocyclic alkenesulfonic acids obtained were analysed by high-temperature molecular dynamics and DFT calculations. Thioglycosides bearing a sulfonatomethyl moiety at the secondary position have been prepared for the first time. Finally, the attempted synthesis of 2-sulfonatomethyl glucoside by nucleophilic substitution reaction is also described.
- Published
- 2016
50. Isolation, Stereochemical Study, and Antioxidant Activity of Benzofuranone Derivatives from a Mangrove-derived FungusEurotium rubrumMA-150
- Author
-
Yang Liu, Xiao-Ming Li, Ling-Hong Meng, Bin-Gui Wang, Tibor Kurtán, and Attila Mándi
- Subjects
Pharmacology ,Circular dichroism ,Antioxidant ,biology ,010405 organic chemistry ,Stereochemistry ,DPPH ,medicine.medical_treatment ,Organic Chemistry ,Absolute configuration ,Fungus ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,medicine ,Density functional theory ,Enantiomer ,Chirality (chemistry) ,Spectroscopy - Abstract
Enantiomers of a 2-benzofuran-1(3H)-one derivative [(-)-1 and (+)-1] and four known analogs (2, 3, 4, 5) were isolated and identified from the culture extract of Eurotium rubrum MA-150, a fungus obtained from the mangrove-derived rizospheric soil. Their structures were established by detailed interpretation of nuclear magnetic resonance (NMR) data and the structure of (+/-)-1 was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of the enantiomers (-)-1 and (+)-1 was determined by means of online high-performance liquid chromatography - electronic circular dichroism (HPLC-ECD) measurements and time-dependent Density Functional Theory - electronic circular dichroism (TDDFT-ECD) calculations. Compounds (+/-)-1 as well as 2 and 3 exhibited potent DPPH radical scavenging activities with IC50 values of 1.23, 2.26, and 3.99 g/mL, respectively. Chirality 28:581-584, 2016. (c) 2016 Wiley Periodicals, Inc.
- Published
- 2016
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